BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Center for RNA Biomedicine - ECPv6.15.17//NONSGML v1.0//EN CALSCALE:GREGORIAN METHOD:PUBLISH X-WR-CALNAME:Center for RNA Biomedicine X-ORIGINAL-URL:https://rna.umich.edu X-WR-CALDESC:Events for Center for RNA Biomedicine REFRESH-INTERVAL;VALUE=DURATION:PT1H X-Robots-Tag:noindex X-PUBLISHED-TTL:PT1H BEGIN:VTIMEZONE TZID:America/Detroit BEGIN:DAYLIGHT TZOFFSETFROM:-0500 TZOFFSETTO:-0400 TZNAME:EDT DTSTART:20200308T070000 END:DAYLIGHT BEGIN:STANDARD TZOFFSETFROM:-0400 TZOFFSETTO:-0500 TZNAME:EST DTSTART:20201101T060000 END:STANDARD BEGIN:DAYLIGHT TZOFFSETFROM:-0500 TZOFFSETTO:-0400 TZNAME:EDT DTSTART:20210314T070000 END:DAYLIGHT BEGIN:STANDARD TZOFFSETFROM:-0400 TZOFFSETTO:-0500 TZNAME:EST DTSTART:20211107T060000 END:STANDARD BEGIN:DAYLIGHT TZOFFSETFROM:-0500 TZOFFSETTO:-0400 TZNAME:EDT DTSTART:20220313T070000 END:DAYLIGHT BEGIN:STANDARD TZOFFSETFROM:-0400 TZOFFSETTO:-0500 TZNAME:EST DTSTART:20221106T060000 END:STANDARD BEGIN:DAYLIGHT TZOFFSETFROM:-0500 TZOFFSETTO:-0400 TZNAME:EDT DTSTART:20230312T070000 END:DAYLIGHT BEGIN:STANDARD TZOFFSETFROM:-0400 TZOFFSETTO:-0500 TZNAME:EST DTSTART:20231105T060000 END:STANDARD BEGIN:DAYLIGHT TZOFFSETFROM:-0500 TZOFFSETTO:-0400 TZNAME:EDT DTSTART:20240310T070000 END:DAYLIGHT BEGIN:STANDARD TZOFFSETFROM:-0400 TZOFFSETTO:-0500 TZNAME:EST DTSTART:20241103T060000 END:STANDARD END:VTIMEZONE BEGIN:VEVENT DTSTART;TZID=America/Detroit:20211215T160000 DTEND;TZID=America/Detroit:20211215T170000 DTSTAMP:20260403T141002 CREATED:20210901T192352Z LAST-MODIFIED:20210901T192352Z UID:9335-1639584000-1639587600@rna.umich.edu SUMMARY:RNA Collaborative Seminar Series // Host: Harvard Medical School Initiative for RNA Medicine DESCRIPTION:For the seminar details\, visit: https://www.rnasociety.org/rna-collaborative-seminar-series URL:https://rna.umich.edu/events/rna-collaborative-seminar-series-host-harvard-medical-school-initiative-for-rna-medicine/ END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20211220T160000 DTEND;TZID=America/Detroit:20211220T170000 DTSTAMP:20260403T141002 CREATED:20210827T134635Z LAST-MODIFIED:20211210T212954Z UID:9277-1640016000-1640019600@rna.umich.edu SUMMARY:RNA Faculty Candidate Seminar: Dr. Alisha 'Jonesy' Jones\, Institute of Structural Biology\, Helmholtz Zentrum Munich DESCRIPTION:“Modulation of the MALT1 pre-mRNA structure by hnRNP proteins regulates T cell activation”\nDr. Alisha ‘Jonesy’ Jones\nPostdoctoral Researcher\nInstitute of Structural Biology\nHelmholtz Zentrum Munich \n  \n  \nFlyer in PDF \nCo-Hosts: The Center for RNA Biomedicine\, Department of Biological Chemistry\, and the Program in Biophysics \nHybrid Seminar:\nIn-person: Biomedical Science Research Buliding (BSRB)\, ABC Seminar rooms\nZoom: https://umich.zoom.us/webinar/register/WN_3yrQ47UuTKKuzigbe38Sww \nKeywords: pre-mRNA\, hnRNP\, NMR\, SHAPE\, structure \nAbstract: Alternative splicing is controlled by differential binding of trans-acting RNA binding proteins (RBPs) to cis-regulatory pre-mRNA elements. How pre-mRNA secondary structure affects recognition by RBPs and determines alternative exon usage is poorly understood. The MALT1 paracaspase is a key component of signaling pathways that mediate innate and adaptive immune responses. Alternative splicing of MALT1 exon7 is critical for controlling optimal T cell activation. Here\, we demonstrate that MALT1 pre-mRNA splicing depends on RNA structural elements that shield the splice sites of the alternatively spliced exon7. The RBPs hnRNP U and hnRNP L bind comparably and competitively to identical stem-loop RNA structures flanking the 5’ and 3’ splice sites of MALT1 exon7. While hnRNP U stabilizes RNA stem-loop conformations that maintain exon7 skipping\, hnRNP L destabilizes these RNA elements to facilitate recruitment of the essential splicing factor U2AF2 to promote exon7 inclusion. This work represents a paradigm for the control of splice site selection by differential RBP binding and modulation of pre-mRNA structure. \nIn-person event COVID guidelines URL:https://rna.umich.edu/events/alisha-jonesy-jones/ CATEGORIES:Seminar END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20220110T160000 DTEND;TZID=America/Detroit:20220110T170000 DTSTAMP:20260403T141002 CREATED:20211130T161429Z LAST-MODIFIED:20220105T212127Z UID:9805-1641830400-1641834000@rna.umich.edu SUMMARY:RNA Faculty Candidate Seminar: Rachel Niederer\, Yale School of Medicine DESCRIPTION:“Uncovering novel translational control elements within 5′ UTRs”\nRachel Niederer\, Ph.D.\nPostdoctoral Researcher\nYale School of Medicine \n  \nCo-Hosts: The Center for RNA Biomedicine\, Department of Biological Chemistry\, and the Department of Human Genetics \nHybrid Seminar:\nIn-person: Biomedical Science Research Buliding (BSRB)\, ABC Seminar rooms\nZoom: https://umich.zoom.us/webinar/register/WN_qg4fyCUbQZyVu0oGrBLmWQ \nAbstract: Translational control of gene expression plays an essential role during development\, response to stress and a wide range of cellular processes. However\, the key mRNA features that distinguish efficiently translated from poorly translated mRNAs remain largely unknown. This talk will describe the development of direct analysis of ribosome targeting (DART) and its use both in discovering novel regulatory elements within 5′ untranslated regions (5′ UTRs) as well as revealing unexpected behaviors from features that were previously thought to be well understood. \nIn-person event COVID guidelines \nFlyer in PDF URL:https://rna.umich.edu/events/rachel-niederer/ CATEGORIES:Seminar END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20220131T160000 DTEND;TZID=America/Detroit:20220131T170000 DTSTAMP:20260403T141002 CREATED:20211130T164405Z LAST-MODIFIED:20220104T163046Z UID:9808-1643644800-1643648400@rna.umich.edu SUMMARY:RNA Faculty Candidate Seminar: Jailson (Jay) Brito Querido\, MRC Laboratory of Molecular Biology DESCRIPTION:“The scanning mechanism of mRNA translation initiation in humans”\nJailson (Jay) Brito Querido\, Ph.D.\nPostdoctoral Scientist\nMRC Laboratory of Molecular Biology\nCambridge\, UK \n  \n  \n  \nCo-Hosts: The Center for RNA Biomedicine\, Department of Biological Chemistry\, and the Program in Biophysics \nHybrid Seminar:\nIn-person: Biomedical Science Research Building (BSRB)\, ABC Seminar rooms\nZoom: https://umich.zoom.us/webinar/register/WN_pcS-fWIdSS-hDnKzoRhXeg \nKeywords: mRNA\, translation\, ribosome\, helicase\nAbstract: Decoding the genetic information into protein is fundamental for all kingdoms of life. It requires precise mechanisms to transcribe the DNA into mRNA\, which then can be translated by the ribosome to produce proteins. Translation initiation of eukaryotic mRNAs is a dynamic process regulated by over a dozen protein eukaryotic initiation factors (eIFs). This process starts with the binding of eukaryotic initiation factors eIF1\, eIF1A\, eIF3\, eIF5\, and a ternary complex of eIF2–GTP–tRNAiMet (TC) to the 40S small ribosomal subunit\, forming the 43S preinitiation complex (43S PIC). Once assembled\, the 43S PIC is recruited to the 5′ untranslated region (UTR) of mRNA by the multifactor cap-binding complex eIF4F\, forming the 48S initiation complex (48S). The 48S then scans along the 5′ UTR mRNA to locate a start codon. The eIF4F binding site in the 48S and how mRNA is inserted into the mRNA channel in the 40S small ribosomal subunit remained unknown. To gain insights into the molecular mechanism underlining the assembly of the 48S\, we used cryo-electron microscopy to determine the structure of a reconstituted human 48S. The structure sheds light on the early events of translation initiation complex assembly\, including how eIF4F interacts with the 43S during the scanning process. \nIn-person COVID Events Policy URL:https://rna.umich.edu/events/jay-brito-querido/ CATEGORIES:Seminar END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20220214T160000 DTEND;TZID=America/Detroit:20220214T170000 DTSTAMP:20260403T141002 CREATED:20211130T173006Z LAST-MODIFIED:20220204T174223Z UID:9812-1644854400-1644858000@rna.umich.edu SUMMARY:RNA Faculty Candidate Seminar: Margaret (Maggie) Rodgers\, Johns Hopkins University DESCRIPTION:“Mechanisms of co-transcriptional ribonucleoprotein assembly”\nMargaret (Maggie) Rodgers\, Ph.D.\nPostdoctoral Researcher\nJohns Hopkins University \n  \n  \n  \n  \nCo-Hosts: The Center for RNA Biomedicine\, Department of Biological Chemistry\, and the Program in Biophysics \nHybrid Seminar:\nIn-person: Biomedical Science Research Buliding (BSRB)\, ABC Seminar rooms\nZoom: https://umich.zoom.us/webinar/register/WN_Icqg8jRbQNGCBEFkj_u5Gw \nKeywords: RNA\, RNP\, ribosome assembly\, transcription\, single-molecule fluorescence \nSeminar flyer in PDF \nIn-person event COVID guidelines URL:https://rna.umich.edu/events/margaret-maggie-rodgers/ CATEGORIES:Seminar END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20220228T160000 DTEND;TZID=America/Detroit:20220228T170000 DTSTAMP:20260403T141002 CREATED:20220214T173408Z LAST-MODIFIED:20220214T212905Z UID:10113-1646064000-1646067600@rna.umich.edu SUMMARY:Seminar: John Prensner\, MD\, PhD DESCRIPTION:“Translating the cancer genome: dark matter proteins”\nJohn Prensner\, M.D.\, Ph.D.\nPhysician\, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center\nInstructor of Pediatrics\, Harvard Medical School \n  \n  \nCo-Hosts: The Center for RNA Biomedicine\, Department of Computational Medicine & Bioinformatics\, and Department of Pediatric Oncology \nHybrid Seminar:\nIn-person: Biomedical Science Research Building (BSRB)\, ABC Seminar rooms\nZoom: https://umich.zoom.us/webinar/register/WN_bC6oy6VZTLy3ke4iMS2sKQ \nKeywords: cancer\, ribosome profiling\, functional genomics\, gene discovery \nAbstract: Although genomic analyses predict many non-canonical open reading frames (ORFs) in the human genome\, it is unclear whether they encode biologically active proteins in diseases such as cancer. Here\, we have developed functional genomics platforms to systematically interrogate non-canonical ORFs identified in ribosome profiling data. Using CRISPR loss-of-function screens in numerous human cancer models\, we define the frequency with which ORFs contribute to cell essentiality phenotypes. We further constructed large-scale ORF plasmid libraries to assess their capacity to encode a protein and induce cancer cell transcriptional changes. We pursued focused investigation of several uncharacterized protein-coding loci\, defining roles for the lncRNA-ORF GREP1 in breast cancer and the ASNSD1 upstream ORF (uORF) in medulloblastoma. Lastly\, we have assembled a pathway to bring such ORF candidates into the mainstream of biological research via an international consortium of gene database stakeholders. Together\, this work establishes non-canonical ORFs as critical mediators of cancer cell biology\, suggests their potential promise as therapeutic targets in cancer\, and outlines a path forward for dissemination of these ORFs amongst the global research community. \nIn-person COVID Events Policy URL:https://rna.umich.edu/events/john-prensner/ CATEGORIES:Seminar END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20220321T150000 DTEND;TZID=America/Detroit:20220321T160000 DTSTAMP:20260403T141002 CREATED:20220314T142057Z LAST-MODIFIED:20220314T183351Z UID:10183-1647874800-1647878400@rna.umich.edu SUMMARY:RNA Therapeutics Seminar\, Michelle Hastings\, Rosalind Franklin University DESCRIPTION:Inaugural RNA Therapeutics Seminar\nMichelle Hastings\, Ph.D.\nProfessor\, Cell Biology and Anatomy; Director\, Center for Genetic Diseases\nRosalind Franklin University of Medicine and Science \n  \n  \n  \nThis is an internal U-M event:\nIn-person: Palmer Commons\, Forum Hall\nZoom: https://umich.zoom.us/webinar/register/WN_mUj40sudTwmI6hXANnlJEg \nKeywords: pre-mRNA splicing\, Antisense oligonucleotides\, Usher syndrome\, Batten Disease\, lysosomal storage diseases \nSeminar flyer in PDF \nIn-person COVID Events Policy URL:https://rna.umich.edu/events/rna-therapeutics-seminar-michelle-hastings/ CATEGORIES:Seminar END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20220325T083000 DTEND;TZID=America/Detroit:20220325T160000 DTSTAMP:20260403T141002 CREATED:20210910T175731Z LAST-MODIFIED:20210910T175921Z UID:9401-1648197000-1648224000@rna.umich.edu SUMMARY:6th Annual RNA Symposium DESCRIPTION:Featured keynote speakers\nChris Burge\, MIT\nMichelle Hastings\, Rosalind Franklin University of Medicine and Science\nJohn Rinn\, University of Colorado-Boulder\nGisela Storz\, NIH\nJack Szostak\, University of Chicago \nFor more details\, visit: https://rna.umich.edu/2022-symposium/ \n  \n  \n\n\n \n \n Symposium Registration Form\n \n \n URLThis field is for validation purposes and should be left unchanged.Name*\n \n \n \n First\n \n \n \n \n Last\n \n \n TitleDepartmentEmail*\n \n PhoneWill you attend in-person or via Zoom?*\n \n In-person\n \n \n Zoom\n \n \n Both\n CAPTCHA\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n Δ URL:https://rna.umich.edu/events/6th-annual-rna-symposium/ CATEGORIES:Symposium END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20220328T160000 DTEND;TZID=America/Detroit:20220328T170000 DTSTAMP:20260403T141002 CREATED:20211206T182658Z LAST-MODIFIED:20220319T182647Z UID:9869-1648483200-1648486800@rna.umich.edu SUMMARY:RNA Innovation Seminar: Wendy Gilbert\, Ph.D. DESCRIPTION:“Marvelous U: Canonical and non-canonical functions of uridine modifying enzymes in health and disease”\nWendy Gilbert\, Ph.D.\nAssociate Professor of Molecular Biophysics and Biochemistry\nYale School of Medicine \nFlyer in PDF \n  \n  \n  \nHybrid Seminar\nIn-person: BSRB\, ABC Seminar Rooms\nZoom: https://umich.zoom.us/webinar/register/WN_P6PEipcsRPmG7cAL104K-Q \nKeywords:\nRNA modifications\, RNA processing\, RNA folding\, pre-mRNA\, tRNA\, translation\, cancer \nAbstract:\nRNA modifications are essential for human health—too much or too little leads to serious illnesses ranging from neurodevelopmental disorders to cancer. We are working to uncover the RNA targets of RNA modifying enzymes that are dysregulated in disease and to understand their molecular and organismal roles. Recent advances in detecting the modified nucleosides pseudouridine and dihydrouridine reveal complex landscapes that include pre-messenger RNA and diverse classes of noncoding RNA in yeast and human cells. I will give an update on our progress towards answering three questions: How are specific RNA sites selected for modification and how is this process regulated? What are the molecular consequences of mRNA and non-coding RNA modifications? How do specific defects in RNA metabolism result in organismal phenotypes\, including disease? URL:https://rna.umich.edu/events/wendy-gilbert/ END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20220411T160000 DTEND;TZID=America/Detroit:20220411T170000 DTSTAMP:20260403T141002 CREATED:20211206T183206Z LAST-MODIFIED:20230129T215823Z UID:9872-1649692800-1649696400@rna.umich.edu SUMMARY:RNA Innovation Seminar: Silvi Rouskin\, Ph.D. DESCRIPTION:“Alternative structures of the SARS-CoV-2 RNA genome control gene expression and offer therapeutic strategies”\nSilvi Rouskin\, Ph.D.\nAssistant Professor\nHarvard Medical School \n  \n  \n  \n  \nVirtual Seminar via Zoom: https://umich.zoom.us/webinar/register/WN_zi3UlKucR6G51hEA_33Exg \nKeywords:\nTBA \nAbstract:\nTBA URL:https://rna.umich.edu/events/silvi-rouskin-2022/ END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20220418T120000 DTEND;TZID=America/Detroit:20220418T130000 DTSTAMP:20260403T141002 CREATED:20211206T183726Z LAST-MODIFIED:20220412T180710Z UID:9876-1650283200-1650286800@rna.umich.edu SUMMARY:RNA Innovation Seminar: Paul Magwene\, Ph.D.\, Duke University DESCRIPTION:“Signaling Pathway Variation and Evolutionary Hotspots in the Fungi”\nPaul Magwene\, Ph.D. \nProfessor of Biology\nDirector\, Computational Biology & Bioinformatics (CBB)\nDuke University \n  \nPDF Flier \nHybrid Seminar\nIn-person: BSRB\, ABC Seminar Rooms\nZoom: https://umich.zoom.us/webinar/register/WN_7wk1SlRdQ_e04VnwcjVV7g \nKeywords:\npopulation genomics\, statistical genetics\, gene networks\, microbial pathogenesis \nAbstract:\nEvolutionarily conserved signal transduction pathways\, such as Ras-cAMP-PKA\, calcineurin\, and TOR signaling\, are primary regulators of stress responses and morphogenetic processes across the fungal tree of life. From an evolutionary perspective\, these pathways are expected to be under relatively strong stabilizing selection\, as loss-of-function mutations (LoF) in these pathways typically lead to reduced growth rates and increased sensitivity to environmental stresses. We have carried out comparative population genomic analyses of signaling pathway LoF alleles for multiple fungal species\, and find that several pathways exhibit unusually high frequencies of naturally occurring putative LoF alleles. We discuss the implications of this finding for the evolutionary lability of signaling pathways in the fungi\, and combine information on loss-of-function alleles with related evidence from QTL mapping and experimental evolution studies to identify pathways that may act as “evolutionary hotspots” for adaptation to novel environments. URL:https://rna.umich.edu/events/paul-magwene/ END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20220509T160000 DTEND;TZID=America/Detroit:20220509T170000 DTSTAMP:20260403T141002 CREATED:20211216T202325Z LAST-MODIFIED:20220502T191433Z UID:9963-1652112000-1652115600@rna.umich.edu SUMMARY:RNA Innovation Seminar: Sika Zheng\, UC Riverside\, School of Medicine DESCRIPTION:“Unexpected determinants of neuronal identity and properties: the curious cases of PTBP1\, PTBP2\, and neuronal splicing”\nSika Zheng\, Ph.D. \nAssociate Professor\, Director of Center for RNA Biology and Medicine\nUC Riverside\, School of Medicine \n  \nFlyer in PDF \n  \nVirtual Seminar\nZoom: https://umich.zoom.us/webinar/register/WN_dltbxWdHQ5KrC3rTl4hqLQ \nAbstract:\nAlternative splicing is the major contributor to transcriptome diversity\, but splicing is noisy and to what extend alternative splicing regulation is indispensable for biolgical processes has been controversial. Our studies have revealed the regulation and function of neural-specific splicing in shaping neuronal identity and estalishing neurons’ two unique attributes: 1. Axonogenesis (Only neurons but no other cell types have one and single axon); 2. Neuronal longevity (Neurons are the most long-lived cell types). We show that obtaining these neuronal features is coordinated by RNA binding proteins PTBP1 and PTBP2\, while PTBP1 was suggested by others to be a reprogramming factor of neuronal fate. I will discuss the regulatory mechanism of neural specific splicing underlying neurogensis and maturation. \nReferences:\nZhang M\, Ergin V\, Lin L\, Stork C\, Chen L\, Zheng S. Neuron. 2019 Feb 20;101(4):690-706.e10.\nErgin V\, Zheng S. J Mol Biol. 2020 Jun 26;432(14):4154-4166.\nZheng S. Wiley Interdiscip Rev RNA. 2020 Jul;11(4):e1585.\nLin L\, Zhang M\, Stoilov P\, Chen L\, Zheng S. Neuron. 2020 Sep 23;107(6):1180-1196.e8.\nVuong J\, Ergin V\, Zheng S. Nature Communications (accepted) URL:https://rna.umich.edu/events/sika-zheng/ CATEGORIES:Seminar END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20220516T160000 DTEND;TZID=America/Detroit:20220516T170000 DTSTAMP:20260403T141002 CREATED:20220218T163352Z LAST-MODIFIED:20220506T161447Z UID:10130-1652716800-1652720400@rna.umich.edu SUMMARY:RNA Innovation Seminar: Daniel O’Reilly DESCRIPTION:“An Academic Approach to Oligonucleotide Therapeutics”\nDaniel O’Reilly Ph.D.\, MRSC\nPost-Doctoral Associate\nKhvorova Lab\nRNA Therapeutics Institute\nUniversity of Massachusetts Medical School \nFlyer in PDF \n  \nHYBRID SEMINAR:\nIn-person: BSRC\, ABC seminar rooms\nZoom: https://umich.zoom.us/webinar/register/WN_dM1a1aKVTM2KfwiieutOWg \nKeywords: Oligonucleotides\, Chemical Modifications\, RNA\, Huntington’s Disease \nAbstract: Nucleic acids (NA) are becoming the third major pillar of therapeutic modalities on par with small molecules and biologics. The diversity of NA molecular mechanisms\, ranging from vaccines\, antisense\, short interfering RNA (siRNAs)\, and guide RNA for CRISPR gene editing systems\, enable impact on most aspects of cellular biology and thus human medicine. The foundation behind the recent oligonucleotides’ clinical success is fundamental chemical innovations in RNA stability\, delivery\, and synthesis.\nOligonucleotides are informational drugs; thus\, if chemical architectures supporting safe and efficient delivery to the tissue of interest are achieved\, they can be easily reprogrammed to modulate any gene expression on demand\, creating an opportunity for academic institutions to drive therapeutic innovation. However\, the process is limited by access to oligonucleotide chemistry and synthetic expertise.\nIn the first half of the talk\, I will share the experience of building and running Nucleic Acid Chemistry Center in a context of a large academic institution. The NACC provides access to therapeutic quality screening leads and large manufacturing of preclinical compounds for the academic community. The impact of the NACC and chemical innovation will be discussed in the context of two significant projects. First\, I will discuss the systematic structure-activity relationship study of chemical modifications to modulate RISC loading and cleavage. Screening 1200 siRNA variants allow for defining the chemical and thermodynamic rules for RISC assembly. URL:https://rna.umich.edu/events/daniel-oreilly/ CATEGORIES:Seminar END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20220523T160000 DTEND;TZID=America/Detroit:20220523T170000 DTSTAMP:20260403T141002 CREATED:20211206T190501Z LAST-MODIFIED:20220519T134053Z UID:9882-1653321600-1653325200@rna.umich.edu SUMMARY:RNA Innovation Seminar: Analisa DiFeo & Bambarendage (Pini) Perera DESCRIPTION:HYBRID SEMINAR:\nIn-person: BSRC\, ABC seminar rooms\nLivestream: https://umich.zoom.us/webinar/register/WN_mXMOsCvlQrSyuJQO0_EnWw \n \n“A miRNA-mediated approach to dissect the complexity of cancer progression and identify anti-cancer drugs”\nAnalisa DiFeo\, Ph.D.\nAssociate Professor\nPathology and Ob/Gyn\nMichigan Medicine \nAbstract: High grade serous carcinoma (HGSC) the most common type of “ovarian” cancer is one of the deadliest cancers diagnosed in women. One of the primary drivers for the high mortality rate associated with HGSC is tumor recurrence and chemoresistance. Thus\, there is a critical need to identify the genetic drivers of tumor development and recurrence to improve therapeutic strategies. In this proposal\, we provide extensive evidence for the clinical and biological importance of miR-181a\, which is amplified in a large majority of HGSC patients\, correlates with poor overall survival\, and induces epithelial to mesenchymal transition (EMT)\, metastasis\, drug resistance\, and stem-like cell properties. Remarkably\, this correlation between miR-181a with clinical outcome and recurrence has also been shown in numerous other cancers. Notably\, miR-181a expression in HGSC tumors offered stronger prognostic value than established clinical biomarkers. Furthermore\, analysis of >10\,000 tumors representing 20 different cancers revealed that amplification of miR-181a correlated with poor outcome. Most recently\, we have uncovered a novel mechanism through which miR-181a can drive tumor development at the earliest stage through the cooperative targeting of RB1 and Stimulator of Interferon Genes (STING). Enhanced miR-181a promoted the growth of highly aggressive and genomically instable cells through the direct inhibition of STING\, a key activator of interferon signaling in response to cytoplasmic DNA. Though activating anti-tumor immunity is increasingly being recognized as an important therapy in cancer treatment the efficacy of current immunotherapies for the treatment of HGSC has not been successful mainly due to the highly immunosuppressive microenvironment. One of the primary means by which a tumor creates an immunosuppressive microenvironment is by inhibiting STING signaling within the tumor. Thus\, our novel finding showing that miR-181a directly regulates STING introduced unique opportunity to assess whether therapeutic targeting of the miR-181a will reactivate IFN signaling via STING to overcome immune tolerance that is commonly seen in HGSC tumors. \n  \n\n“The Role of piRNA in Environmental Epigenetics”\nBambarendage Pinithi Perera\, Ph.D.\nResearch Assistant Professor\nEnvironmental Health Sciences\nSchool of Public Health \nKeywords: piRNA\, epigenetics\, toxicology \nAbstract: Piwi-interacting RNAs (piRNAs) are small non-coding RNAs that associate with PIWI proteins to induce DNA methylation for retrotransposon suppression. Mature germline piRNAs typically consist of 24–32 nucleotides with a strong preference for a 5ʹ uridine\, an adenine at position 10\, and a 2ʹ-O-methylated 3ʹ end. In the current study\, we identified piRNAs and associated machinery from mouse somatic tissues by quantifying Piwil1\, Piwil2\, and Piwil4 expression in brain\, liver\, kidney\, and heart. The study revealed 26 piRNA sequence species and 40 piRNA locations exclusive to all examined somatic tissues. Non-coding RNA expression is sensitive to environmental exposures\, although it has been unclear whether exposures such as lead (Pb) impact piRNA expression. In the current study\, mouse dams were exposed to Pb 2 weeks prior to mating which continued through offspring weaning. We profiled tissue- and sex-specific effects of perinatal Pb exposure on the piRNA transcriptomes of the resulting progeny at 5 months. Based on significant p-values (<0.05)\, 346 piRNAs were differentially expressed among Pb-exposed mice in testes\, 339 in ovaries\, 127 in M cortex\, 105 in F cortex\, 42 in M liver\, and 59 in F liver. According to preliminary results\, a total of 3 piRNAs were\ndifferentially expressed based on FDR(q<0.05). Although piRNA expression has long been considered exclusive to the germline\, our results support previous reports of somatic piRNA expression\, and demonstrate that perinatal environmental exposures such as Pb influence longitudinal piRNA expression in a tissue- and sex-specific manner. \n  \n  URL:https://rna.umich.edu/events/difeo-and-perera/ END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20220606T160000 DTEND;TZID=America/Detroit:20220606T170000 DTSTAMP:20260403T141002 CREATED:20211206T182024Z LAST-MODIFIED:20220531T153226Z UID:9864-1654531200-1654534800@rna.umich.edu SUMMARY:RNA Innovation Seminar: Selene L. Fernandez-Valverde\, Ph.D. DESCRIPTION:“Long non-coding RNAs as evolutionarily fluid chromatin weavers”\nSelene L. Fernandez-Valverde\, Ph.D.\nPrincipal Investigator\nAdvanced Genomics Unit\nLANGEBIO\, Cinvestav \n  \nFlyer in PDF \nHYBRID SEMINAR:\nIn-person: BSRB\, ABC seminar rooms\nZoom: https://umich.zoom.us/webinar/register/WN_3ga-wcUYSgqPEKw57DSfpg \nKeywords: lncRNAs\, Genomics\, Genome topology \nAbstract: Long non-coding RNAs (lncRNAs) have recently emerged as prominent elements of the regulatory transactions of eukaryotic genomes. Many of the know regulatory functions of lncRNAs in both animals and plants rely on the rearrangement of chromatin through direct interactions or recruitment of chromatin-modifying elements. In this talk\, I will discuss the difficulty in identifying evolutionary conservation in lncRNAs\, and how we characterize these evolutionarily volatile elements in the context of their role as regulators of the three-dimensional conformation of nuclear chromatin. I will focus on our findings resulting from the concurrent characterization of transcripts\, tridimensional chromatin structure and direct RNA-DNA interactions in closely related plant species. I will also discuss how such techniques have vast potential to illuminate biomedically relevant lncRNAs when analyzed from a comparative genomics perspective. URL:https://rna.umich.edu/events/selene-fernandez-valverde/ END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20220912T160000 DTEND;TZID=America/Detroit:20220912T170000 DTSTAMP:20260403T141002 CREATED:20220826T123641Z LAST-MODIFIED:20220829T141846Z UID:10539-1662998400-1663002000@rna.umich.edu SUMMARY:RNA Innovation Seminar: Zhipeng Lu\, USC DESCRIPTION:“RNA Structures\, Interactions and Modifications”\nZhipeng Lu (鲁志鹏)\, Ph.D.\nAssistant Professor\nPharmacology and Pharmaceutical Sciences\nUniversity of Southern California \n  \nFlyer in PDF \nIn-person: BSRB\, ABC seminar rooms / hybrid link \nAbstract: RNA in living cells are in constant motion\, form dynamic structures\, and interact with many molecules\, including other RNAs. Direct determination of RNA structures and interactions in vivo is essential to understanding their functions\, but has been challenging in the past. We developed a number of novel chemical and computational tools to capture the 2D and 3D RNA structurome and interactome in cells\, providing a comprehensive view of RNA conformations that underlie their roles in gene regulation and human diseases. Applications of these methods revealed new mechanisms in lncRNA functions\, RNA modifications and splicing regulation. URL:https://rna.umich.edu/events/zhipeng-lu/ CATEGORIES:Seminar END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20220926T160000 DTEND;TZID=America/Detroit:20220926T170000 DTSTAMP:20260403T141002 CREATED:20220902T184752Z LAST-MODIFIED:20220906T131746Z UID:10554-1664208000-1664211600@rna.umich.edu SUMMARY:RNA Innovation Seminar: David Shechner\, University of Washington DESCRIPTION:“Meet the neighbors: A universal technology for probing RNA-interactions and RNA-scaffolded subcellular compartments in situ”\nDavid Shechner Ph.D.\nAssistant Professor of Pharmacology\nUniversity of Washington \n  \nFlyer in PDF \nIn-person: BSRB\, ABC seminar rooms / hybrid link \nKeywords: RNA\, proximity-biotinylation\, subcellular architecture\, nuclear architecture\, spatial biology\, biomolecular condensates\, interactomics\, nucleolus\, Xist. \n  \nAbstract: In the context of the living cell\, very little RNA is naked. RNA molecules form complex\, dynamic networks of molecular interactions that underlie a host of biochemical functions\, and which are central to organizing subcellular compartmentalization. In humans\, for example\, RNAs are key determinants of chromatin folding\, and they nucleate and scaffold a host of biomolecular condensates that collectively control cellular metabolic\, epigenetic\, and stress-signaling pathways. But\, characterizing these structures—identifying the biomolecules within an RNA’s subcellular microenvironment—remains technically cumbersome. \nTo address this challenge\, I introduce oligonucleotide-mediated proximity-interactome mapping (O-MAP)\, a straightforward and flexible method for identifying the proteins\, RNAs\, and genomic loci near a target RNA\, within its native cellular context. O-MAP uses programmable oligonucleotide probes to deliver proximity-biotinylating enzymes to a target RNA. These enzymes then pervasively label all nearby (~20 nm) molecules\, enabling their enrichment by streptavidin pulldown. O-MAP induces exceptionally precise RNA-targeted biotinylation\, and its modular design enables straightforward validation of probe pools and real-space optimization of the biotinylation radius\, thus overcoming key technical challenges for the field. Moreover\, O-MAP can be readily ported across different target RNAs and specimen types\, including patient-derived organoids and tissue samples. And\, O-MAP achieves this without complex cell-line engineering\, using only off-the-shelf parts and standard manipulations. \nUsing a small cohort of model RNAs\, we have developed a robust O-MAP toolkit for proteomic (O-MAP-MS)\, transcriptomic (O-MAP-Seq) and genome interaction (O-MAP-ChIP) discovery. O-MAP of the 47S-pre-rRNA—the long noncoding RNA that scaffolds the nucleolus—enabled a comprehensive “multi-omic” analysis of this subnuclear structure\, and revealed hundreds of novel nucleolar protein-\, RNA-\, and chromatin interactions. O-MAP of XIST—the master regulator of X-chromosome inactivation—revealed novel RNAs that may play a role in this process\, and unanticipated interactions between XIST and other chromatin-regulatory RNAs. Finally\, targeting O-MAP to introns within a key cardiac developmental gene enabled unprecedented molecular dissection of a subnuclear compartment that would be impossible to purify biochemically. \nGiven these results\, we believe that O-MAP will be a powerful tool for elucidating the mechanisms by which RNA molecules drive subcellular compartmentalization in time and space\, with particular impact on our understanding of nuclear architecture. Moreover\, with O-MAP’s precision\, flexibility\, and ease\, we anticipate its broad use in studying countless other RNA phenomena throughout biology\, and as a clinical diagnostic- and discovery tool. URL:https://rna.umich.edu/events/david-shechner/ CATEGORIES:Seminar END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20221010T160000 DTEND;TZID=America/Detroit:20221010T170000 DTSTAMP:20260403T141002 CREATED:20220902T191232Z LAST-MODIFIED:20220920T185235Z UID:10559-1665417600-1665421200@rna.umich.edu SUMMARY:RNA Innovation Seminar: Polly Hsu\, Michigan State University DESCRIPTION:“Roadblocks on mRNAs? Gene Expression Regulation by Upstream Open Reading Frames in Plants”\nPolly Hsu\, Ph.D.\nAssistant Professor\nBiochemistry and Molecular Biology\nMichigan State University \n  \n  \nFlyer in PDF \nIn-person: BSRB\, ABC seminar rooms / hybrid link \nKeywords: translation\, uORFs\, nonsense-mediated decay \nAbstract: 30-70% of mRNAs in humans\, mice and plants contain short ORFs\, called upstream ORFs (uORFs)\, in their 5’ leader sequences. The translation of uORFs is expected to repress the protein synthesis of their downstream main ORF (mORF) and to trigger mRNA degradation\, presumably through nonsense-mediated decay (NMD). I will share our current progress investigating the global and gene-specific mechanisms by which uORFs regulate gene expression in Arabidopsis and tomato. I will discuss 1) different classes of uORFs revealed by Ribo-seq\, 2) the roles of uORFs on transcription factor and protein kinase genes\, 3) the mRNA stability of uORF-containing genes\, and 4) cellular regulatory mechanisms to include or avoid uORFs on mRNA sequences. URL:https://rna.umich.edu/events/polly-hsu/ CATEGORIES:Seminar END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20221017T160000 DTEND;TZID=America/Detroit:20221017T170000 DTSTAMP:20260403T141002 CREATED:20220902T191827Z LAST-MODIFIED:20221013T144443Z UID:10562-1666022400-1666026000@rna.umich.edu SUMMARY:RNA Therapeutics Seminar: John Cooke\, M.D.\, Ph.D.\, Medical Director\, Center for RNA Therapeutics\, Houston Methodist DESCRIPTION:“The Democratization of RNA Therapeutics”\nJohn Cooke\, M.D.\, Ph.D.\nJoseph C. “Rusty” Walter and Carole Walter Looke Presidential Distinguished Chair in Cardiovascular Disease Research\, Department of Cardiovascular Sciences\nChair\, Department of Cardiovascular Sciences\nProfessor of Cardiovascular Sciences\, Academic Institute\nFull Member\, Research Institute\nDirector\, Center for Cardiovascular Regeneration\nMedical Director\, Center for RNA Therapeutics\nHouston Methodist \n  \nFlyer in PDF \nIn-person: BSRB\, ABC room with zoom option \nAbstract: mRNA therapeutics is a disruptive therapeutic technology\, as small biotech startups\, as well as academic groups\, can rapidly develop new and personalized mRNA constructs. In the Texas Medica Center\, we have established a Center for RNA Therapeutics that comprises faculty innovators\, as well as a translational assembly line to bring great RNA ideas to life. Academic groups and small companies work with us as we innovate\, design\, synthesize\, purify\, encapsulate and test mRNA therapies. In addition to providing pre-clinical GLP testing\, we have established cGMP-compliant manufacturing capability and quality control methods to support pre-clinical GLP studies and phase I clinical trials; and have a first-in-man phase 1 clinical trial unit. To support phase II and phase III trials\, and commercialization\, we have licensed our proprietary manufacturing processes to VGXI Inc\, a local company with large-batch manufacturing capabilities for DNA-based gene therapies. With this collaboration\, we have built a seamless transition for academic groups and small companies to go from pre-clinical development and first-in-man clinical trials supported by our hospital-based program\, to late-stage clinical trials and commercialization supported by our industry partner VGXI\, Inc. \n  \nFlyer in PDF URL:https://rna.umich.edu/events/john-cooke/ END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20221121T160000 DTEND;TZID=America/Detroit:20221121T170000 DTSTAMP:20260403T141002 CREATED:20220902T192913Z LAST-MODIFIED:20221111T170833Z UID:10572-1669046400-1669050000@rna.umich.edu SUMMARY:RNA Innovation Seminar: Jeremy Schroeder\, Biological Chemistry DESCRIPTION:“RNA:DNA hybrids cause genome instability through nucleobase deamination\, genomic rearrangements\, and induction of the DNA damage response”\nJeremy Schroeder\, Ph.D.\nResearch Investigator\nBiological Chemistry\nUniversity of Michigan \n  \n  \nIn-person: BSRB\, ABC seminar rooms / hybrid link \nAbstract: The overall impacts of naturally occurring RNA:DNA hybrids on genome integrity\, and the relative contributions of ribonucleases H to mitigating the negative effects of these hybrids\, remain unknown. Here\, we use the model bacterium Bacillus subtilis to investigate the contribution of RNases HII (RnhB) and HIII (RnhC) to hybrid removal\, DNA replication\, and mutagenesis genome-wide. Deletion of either rnhB or rnhC alters RNA:DNA hybrid formation\, but with distinct patterns of mutagenesis and hybrid accumulation. For ΔrnhB\, hybrids form preferentially in genes transcribed co-directionally with DNA replication. For ΔrnhC\, hybrids accumulate in all genes regardless of their orientation\, and DNA replication is disrupted leading to transversions and structural variation. We find that base deamination in the displaced strand of an R-loop leads to transition mutations in coding sequences\, independent of gene orientation. Our results resolve the outstanding question of how hybrids in native genomic contexts interact with replication to cause mutagenesis. URL:https://rna.umich.edu/events/jeremy-schroeder/ END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20221205T160000 DTEND;TZID=America/Detroit:20221205T170000 DTSTAMP:20260403T141002 CREATED:20220902T194437Z LAST-MODIFIED:20221128T001805Z UID:10583-1670256000-1670259600@rna.umich.edu SUMMARY:RNA Innovation Seminar: Francesca Luca\, Wayne State University DESCRIPTION:“Genetic\, environmental\, and developmental factors in immune cell gene expression and asthma”\nFrancesca Luca\, Ph.D.\nProfessor\nCenter for Molecular Medicine and Genetics\nWayne State University \n  \n  \nIn-person: BSRB\, ABC seminar rooms / hybrid link \nAbstract: Asthma is an immunological disorder with genetic and environmental components. In the last ten years we have been studying genetic and environmental factors that contribute to asthma severity in children living in the metropolitan Detroit area\, as part of the NHLBI funded project: Asthma in the Lives of Families Today (ALOFT). We have performed bulk and single cell RNA-sequency in this cohort and uncovered psychosocial and genetic factors associated with asthma. I will present our findings on the dynamic genetic regulation of gene expression in response to immunomodulators and during pubertal development. I will also discuss the importance of considering environmental and developmental contexts when using molecular data to study the genetic risk of asthma and other complex traits. \nKeywords: Gene expression\, gene-environment interactions\, eQTL\, asthma\, single cell genomics URL:https://rna.umich.edu/events/francesca-luca/ END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20221219T120000 DTEND;TZID=America/Detroit:20221219T130000 DTSTAMP:20260403T141002 CREATED:20221118T154320Z LAST-MODIFIED:20221220T131454Z UID:10695-1671451200-1671454800@rna.umich.edu SUMMARY:RNA Therapeutics Seminar: Melissa Moore\, CSO\, Moderna Therapeutics\, Emerita DESCRIPTION:“The Science Behind mRNA Medicines: COVID-19 Vaccines and Beyond”\nMelissa J. Moore\, Ph.D.\nChief Scientific Officer\, Moderna Therapeutics\, Emerita\nIn-person: BSRB\, Kahn Auditorium and hybrid. Here is the link for the seminar video. \nDr. Moore will be awarded an honorary degree at the University of Michigan Ann Arbor campus’ 2022 Winter Commencement and give this scientific talk to our RNA community. \n  \n  \nBiography: From 2016-2021\, Dr. Moore led the early-stage research teams developing Moderna’s platform technologies in mRNA design and delivery. These technologies were foundational for Moderna’s ability to rapidly create a highly effective vaccine against SARS-CoV-2. As CSO\, Emerita\, she now focuses on explaining the science behind mRNA medicines. During her 23 years as faculty member\, first at Brandeis University (1994-2007) and then at the University of Massachusetts Medical School (2007-2016)\, her research encompassed a broad array of topics related to the roles of RNA and RNA-protein (RNP) complexes in gene expression\, and touched on many human diseases including cancer\, neurodegeneration and preeclampsia. A long-time Investigator at the Howard Hughes Medical Institute (HHMI)\, Dr. Moore is an elected member of the National Academy of Sciences (2017)\, a Fellow of the American Academy of Arts and Sciences (2019)\, and recipient of the RNA Society Lifetime Achievement Award (2021).\nDr. Moore holds a B.S. in Chemistry and Biology from the College of William and Mary\, and a Ph.D. in Biological Chemistry from MIT\, where she specialized in enzymology under Prof. Christopher T. Walsh. She bean working on RNA metabolism during her postdoctoral training with Philip A. Sharp at MIT. Her passions include educating the public about the coming age of nucleic acid medicines and increasing Diversity\, Equality and Inclusion (DEI) at all levels of the biotechnology workforce. URL:https://rna.umich.edu/events/melissa-moore-2022/ END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20221219T160000 DTEND;TZID=America/Detroit:20221219T170000 DTSTAMP:20260403T141002 CREATED:20220902T193934Z LAST-MODIFIED:20221219T204928Z UID:10579-1671465600-1671469200@rna.umich.edu SUMMARY:RNA Innovation Seminar: Hayley McLoughlin\, Neurology DESCRIPTION:“Antisense Oligonucleotides for Ataxia”\nHayley McLoughlin\, Ph.D.\nAssistant Professor of Neurology\nAssistant Professor of Human Genetics\nUniversity of Michigan \n  \n  \nIn-person: BSRB\, ABC seminar rooms / hybrid link \nAbstract: Her talk will cover recent advances in antisense oligonucleotide (ASO) therapy with a particular emphasis towards their mechanistic and therapeutic applications in Ataxia. She will specifically discuss ASO approaches in the most common dominantly inherited ataxia\, Spinocerebellar ataxia type (SCA3). SCA3 is one of nine polyglutamine expansion diseases and is caused by a gain-of-function repeat expansion in the disease gene\, ATXN3. To date\, there is no effective treatment for this relentlessly progressive and fatal neurodegenerative disease. Throughout her postdoctoral training in Dr. Paulson’s lab and into her independent research career\, she has assessed the efficacy and tolerability of anti-ATXN3 ASO gene silencing therapy in SCA3 mouse models in collaboration with Ionis Pharmaceuticals. Published in successive cross-sectional (PMC5415970) and longitudinal studies (PMC6119475)\, they defined the first evidence of a gene therapy mitigating both pathological and behavioral disease phenotypes in the SCA3 mouse\, which overexpresses the full-length human disease gene. These anti-ATXN3 ASOs are currently begin assessed in SCA3 human subjects through a Phase 1 clinical trial driven by Biogen for pharmacokinetics and safety (ClinicalTrials.gov Identifier: NCT05160558). URL:https://rna.umich.edu/events/hayley-mcloughlin/ END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20230109T160000 DTEND;TZID=America/Detroit:20230109T170000 DTSTAMP:20260403T141002 CREATED:20220902T192057Z LAST-MODIFIED:20230109T135614Z UID:10565-1673280000-1673283600@rna.umich.edu SUMMARY:RNA Innovation Seminar: Karen Mohlke\, UNC DESCRIPTION:“Genetic Variant Effects on Adipose Gene Expression and Their Role in Cardiometabolic Traits.”\nKaren Mohlke\, Ph.D.\nProfessor and Associate Chair for Research\nOliver Smithies Investigator\nDepartment of Genetics\, University of North Carolina\nIn-person: BSRB\, ABC seminar rooms / hybrid link \nAbstract: Noncoding genetic variants can affect common diseases and related quantitative traits. Variants may affect the expression levels of transcripts and alternatively-spliced isoforms\, dependent on cell context. I will describe genetic variants associated with adipose tissue gene expression level in >2\,200 people and their putative roles in cardiometabolic disease traits. Similarly\, I will implicate variants associated with splice junction usage in disease risk. Finally\, based on chromatin accessibility during adipocyte differentiation\, I will show genetic regulatory effects that depend on cell context. Together\, these studies help identify regulatory mechanisms for common diseases.\nKeywords: Transcriptome\, expression quantitative trait loci (eQTL)\, splice QTL (sQTL)\, genome-wide association study (GWAS)\, chromatin accessibility\, epigenome\, adipose tissue\, adipocyte. URL:https://rna.umich.edu/events/karen-mohlke/ END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20230130T160000 DTEND;TZID=America/Detroit:20230130T170000 DTSTAMP:20260403T141002 CREATED:20221102T121834Z LAST-MODIFIED:20230110T144621Z UID:10666-1675094400-1675098000@rna.umich.edu SUMMARY:RNA Innovation Seminar: Carlos Cruchaga\, Washington University in St Louis DESCRIPTION:“Role of Circular RNA in Alzheimer’s Disease”\nCarlos Cruchaga\, Ph.D.\nDirector\, NeuroGenomics and Informatics Center\nWashington University in St Louis\nIn-person: BSRB\, ABC seminar rooms / hybrid link \nShort Bio: Dr. Cruchaga is a human genomicist with expertise in multiomics\, informatics\, and neurodegeneration. He completed his PhD in Biochemistry & Molecular Biology in 2005 at the University of Navarra in Spain. During his first postdoc with Dr. Pastor he conducted statistical human genetics studies focused on Alzheimer’s disease (AD) and Parkinson’s disease (PD). He then moved to Dr. Goate’s Lab to complete his training in quantitative human genomics. Dr Cruchaga established his laboratory at Washington University in  2011 to study the genetic architecture of neurodegenerative diseases. His interests are focused on using human genomic and other -omis data (proteomics\, metabolomics\, & lipidomics) to identify and understand the biological processes that lead to AD\, PD\, frontotemporal dementia\, and other neurodegenerative processes. He is the founding director of the NeuroGenomics and Informatics Center at Washington University. \nAbstract: Circular RNAs (circRNAs) are a class of RNAs highly expressed in the nervous system and enriched in synaptoneurosomes. In Alzheimer Disease\, synapse lost is one of the events implicated on disease. circRNA are form by back-splicing (head-to-tail splicing)\, and where first described in eukaryotic cells and other studies suggested that synapse could be enriched for circRNA. Based on we hypothesized that specific circRNA would be differentially expressed in AD cases compared to controls and that those effects could be detected early in the disease. We optimized and validated a novel analyses pipeline for circular RNAs (circRNA). We performed a three-stage study design to robustly identify circRNA associated with AD and AD-related phenotypes. Additional analyses were performed to demonstrate that the expression of circRNA were independent of the lineal form as well as the cell proportion that can confound results. Co-expression analyses of all the circRNA together with the lineal forms and found that circRNA\, including those that were differentially expressed in Alzheimer disease compared to controls co-expressed with known causal Alzheimer genes\, such as APP and PSEN1\, indicating that some circRNA are also part of the causal pathway. We also demonstrated that cirRNAs brain expression explained more about Alzheimer clinical manifestations that the number of APOε4 alleles\, suggesting that could be used as a potential biomarker for Alzheimer disease. In summary\, we demonstrated for the first time that brain circular RNAs (circRNA) are part of the pathogenic events that lead to Alzheimer’s disease URL:https://rna.umich.edu/events/carlos-cruchaga/ END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20230213T120000 DTEND;TZID=America/Detroit:20230213T130000 DTSTAMP:20260403T141002 CREATED:20221102T123120Z LAST-MODIFIED:20230127T141731Z UID:10670-1676289600-1676293200@rna.umich.edu SUMMARY:RNA Innovation Seminar: Gal Haimovich\, Weizmann Institute of Science DESCRIPTION:“Why Did the RNA Cross the Nanotube? Many questions and (some) answers on tunneling-nanotube medicated RNA transfer between mammalian cells”\nGal Haimovich\, Ph.D. \nAssistant Staff Scientist\nDepartment of Molecular Genetics\nWeizmann Institute of Science\nVirtual only: zoom link \nAbstract: RNAs have been shown to undergo transfer between mammalian cells\, though the mechanism behind this phenomenon and its overall importance to cell physiology is not well understood. We found that full-length mRNAs and lncRNAs undergo direct cell-cell transfer via cytoplasmic extensions called tunneling nanotubes (TNTs)\, which connect donor and acceptor cells. Despite 10 years of research\, there are still major questions about this process such as which RNAs are transferred\, what is the mechanism\, how is this process regulated and what does the RNA do on the other side? I will review the evidence for TNT-mediated RNA transfer\, discuss the technical challenges in this field\, and provide some answers to these questions. URL:https://rna.umich.edu/events/gal-haimovich/ END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20230227T160000 DTEND;TZID=America/Detroit:20230227T170000 DTSTAMP:20260403T141002 CREATED:20221102T124955Z LAST-MODIFIED:20230227T210355Z UID:10674-1677513600-1677517200@rna.umich.edu SUMMARY:RNA Innovation Seminar: Jane Jackman\, Ohio State University DESCRIPTION:“A Complicated Family: Conserved & Distinct Functions of tRNA Methyltransferases from Yeast to Humans”\nJane Jackman\, Ph.D.\nProfessor of Chemistry & Biochemistry\nOhio State University\nIn-person: BSRB\, ABC seminar rooms / zoom link \nAbstract: RNA modifications are now known to be a ubiquitous and important feature of cellular RNAs. tRNA are among the most heavily modified of RNA species\, with a large network of often highly conserved enzymes dedicated to introducing distinct modifications into specific subsets of tRNAs in each organism. The expanding number of technological approaches to mapping tRNA modifications has enabled an explosion of information about the types and locations of modifications in many biological systems\, but functional information about many modifications has lagged. The tRNA methyltransferase Trm10 is a SPOUT family RNA methyltransferase that is absolutely conserved throughout Archaea and Eukarya\, but exhibits markedly different substrate specificities for nucleotide and tRNA substrates in different biological contexts. However\, the molecular basis for these distinct substrate specificities has not been demonstrated. Moreover\, despite multiple phenotypes associated with loss of Trm10 N1-methylation\, including a role in human disease\, the biological impact of Trm10 modification is not understood. We have taken a comprehensive approach utilizing enzymes from diverse organisms from Archaea to humans and multiple eukaryotic model systems to identify conserved and unique mechanistic and functional features of this essential family of tRNA methyltransferases. URL:https://rna.umich.edu/events/jane-jackman/ END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20230306T160000 DTEND;TZID=America/Detroit:20230306T160000 DTSTAMP:20260403T141002 CREATED:20221202T145321Z LAST-MODIFIED:20230228T162213Z UID:10717-1678118400-1678118400@rna.umich.edu SUMMARY:RNA Innovation Seminar: Lori Isom\, Chair\, Department of Pharmacology DESCRIPTION:“Dancing to a Different Tune: TANGO Provides Hope for Dravet Syndrome”\nLori Isom\, Ph.D.\nChair\, Department of Pharmacology\nMaurice H. Seevers Collegiate Professor of Pharmacology\nProfessor of Molecular and Integrative Physiology\nProfessor of Neurology\, University of Michigan Medical School\nIn-person: BSRB\, ABC seminar rooms / zoom link \nAbstract: Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by high seizure frequency and severity\, intellectual disability\, and a high risk of sudden unexpected death in epilepsy (SUDEP). Most DS patients carry de novo variants in SCN1A leading to haploinsufficiency of the voltage-gated sodium channel a subunit Nav1.1. Scn1a +/-  DS mouse models recapitulate many patient phenotypes\, including severe seizures and SUDEP. DS mice have reduced excitability of parvalbumin-positive (PV+) fast-spiking interneurons\, leading to disinhibition. Targeted Augmentation of Nuclear Gene Output (TANGO) was developed by our collaborators at Stoke Therapeutics to increase protein expression in diseases of haploinsufficiency using antisense oligonucleotide (ASO) technology. TANGO targets naturally occurring\, non-productive alternative splicing events to reduce non-productive mRNA and increase productive mRNA and protein of the target gene by upregulating the wild-type allele. This approach has provided a unique opportunity to develop novel therapeutics to treat DS. We showed previously that a single\, intracerebroventricular (ICV) dose at postnatal day (P)2 of the ASO STK-001\, generated using TANGO technology to prevent inclusion of a nonsense-mediated decay or poison exon in Scn1a\, exon 20N\, increased productive Scn1a transcript and Nav1.1 expression and reduced the incidence of electrographic seizures and SUDEP in a mouse model of DS (SCIENCE TRANSLATIONAL MEDICINE\, 2020\, Vol 12\, Issue 558\, DOI: 10.1126/scitranslmed.aaz6100). Interestingly\, de novo variants in SCN1A exon 20N were shown by others to increase its inclusion\, resulting in haploinsufficiency and DS pathology in patients and in a mouse model. Our preclinical work led to a series of on-going clinical trials for STK-001. Here\, we investigated the mechanism of a surrogate ASO that also targets exon 20N\, ST-1001\, in DS mouse brain. We tested the effects of a single ICV injection of ST-1001 at P2 on the subsequent electrophysiological properties of cortical pyramidal and PV+ fast-spiking interneurons in Scn1a +/- DS and Scn1a +/+ wild-type littermate control mice at P21-25. We show that\, in untreated DS mice\, intrinsic action potential (AP) firing properties of cortical pyramidal neurons were unchanged compared to controls while AP firing properties of PV+ interneurons showed depolarization block. In addition\, sodium current density was reduced in DS PV+ interneurons. The frequency\, but not amplitude\, of inhibitory post-synaptic currents recorded in DS cortical pyramidal neurons was also reduced\, suggesting reduced GABA release from interneurons. Single-dose ST-1001 ASO administration restored excitability and sodium current density in PV+ DS interneurons as well as restored GABAergic signaling to cortical pyramidal neurons. This new work provides key mechanisms for further development of precision medicine approaches to treat patients with DS and related developmental and epileptic encephalopathies. Our next experimental plan will include testing ST-1001 in a newly developed CRISPR transgenic rabbit model of DS as well as in DS patient-derived induced pluripotent stem cell neurons. URL:https://rna.umich.edu/events/lori-isom/ END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20230410T160000 DTEND;TZID=America/Detroit:20230410T170000 DTSTAMP:20260403T141002 CREATED:20221202T150015Z LAST-MODIFIED:20230403T161646Z UID:10721-1681142400-1681146000@rna.umich.edu SUMMARY:RNA Innovation Seminar: Haiyuan Yu\, Cornell University DESCRIPTION:“Dissect Enhancer Architecture and Map Regulatory Genomic Landscape Across Diverse Cell and Tissue Types Through Nascent Transcriptome Studies”\nHaiyuan Yu\, Ph.D.\nTisch University Professor\nDepartment of Biological Statistics and Computational Biology\nWeill Institute for Cell and Molecular Biology\nDirector\, Center for Innovative Proteomics (CIP@Cornell)\nIn-person: BSRB\, ABC seminar rooms / hybrid link \nAbstract: Recent studies have shown that both enhancers and promoters can recruit RNA pol II and initiate transcription. The short half-life nature of enhancer RNAs (eRNAs) makes detection of distal initiation events challenging. Through systematic comparison of RNA sequencing assays\, we find that nascent transcriptome assays\, PRO-cap and PRO-seq\, have great sensitivity and specificity in detecting eRNA transcription genome-wide. In fact\, we find that\, unlike histone marks\, divergent transcription of eRNAs is a critical mark for all active enhancers genome-wide. Moreover\, nascent transcription precisely delineates the sequence architecture of enhancers\, whereby transcription start sites (TSSs) serve as critical anchors in revealing motif positioning within enhancers and their boundaries. By leveraging our high precision and sensitivity nascent transcriptome PRO-cap and PRO-seq assays\, we mapped the active transcriptional regulatory landscape across ~200 tissue and cell types of the human body with unprecedented resolution and depth. This information is used to quantify gene transcriptional activity and to identify and delineate transcription regulatory elements\, including both enhancers and promoters that are cell-type-specific and ubiquitous. These findings are critical in modeling putative enhancer-promoter connectivity and in speeding the identification of potential disease-associated noncoding variants in regulatory regions. URL:https://rna.umich.edu/events/haiyuan-yu/ END:VEVENT BEGIN:VEVENT DTSTART;TZID=America/Detroit:20230417T160000 DTEND;TZID=America/Detroit:20230417T170000 DTSTAMP:20260403T141002 CREATED:20221202T153751Z LAST-MODIFIED:20230410T185444Z UID:10725-1681747200-1681750800@rna.umich.edu SUMMARY:RNA Innovation Seminar: Julius B. Lucks\, Northwestern University DESCRIPTION:“RNA Synthetic Biology: Towards an Era of RNA Design for Biology & Global Health”\nJulius B. Lucks\, Ph.D.\nProfessor & Associate Chair\, Chemical & Biological Engineering\nCo-Director\, Center for Synthetic Biology\nNorthwestern University\nIn-person: BSRB\, ABC seminar rooms / hybrid link \nAbstract: RNAs are emerging as a powerful substrate for engineering cellular behavior. As with all biomolecules\, RNA function is intimately related to its structure\, since RNA can adopt structures that selectively modulate gene expression. Central questions in biology & bioengineering then are: How do RNAs fold inside cells?; and How can we engineer these folds to control gene expression? In this talk\, I will present our work at the interface of these two questions and share results that are beginning to uncover design principles for understanding natural RNAs and engineering RNAs for an array of applications in biomanufacturing and human health. I will focus on our recent work in understanding how riboswitch RNAs make regulatory decisions “on the fly” during the process of transcription\, how we can use riboswitches as biosensors\, and our recent development of a new synthetic biology biosensing platform that allows rapid\, field-deployable diagnostics for a range of compounds important to our health and the environment. \nRNA\, RNA folding\, RNA synthetic biology\, Riboswitches\, Cell-Free Synthetic Biology URL:https://rna.umich.edu/events/julius-b-lucks/ END:VEVENT END:VCALENDAR