Center for RNA Biomedicine

RNA Innovation Seminar featuring Rising Scholars: Khan & McMillan
2021-06-14 16:00 - 17:00 (America/Detroit)
Registration: https://umich.zoom.us/webinar/register/WN_uLz-ONHVQPuRINMYUNvBJQ
Flyer: Khan & McMillan Seminar flyer

“CCR5 as a model to examine reporter assays in evaluating translational phenomena”
Yousuf Khan
Knight-Hennessy Scholar
NSF fellow
Stanford University

Keywords: dual luciferase, frameshifting, recoding, CCR5
Abstract: During the decoding of a subset of mRNAs, a proportion of ribosomes productively shift to the −1 reading frame at specific slippage-prone sites in a phenomenon known as programmed −1 ribosomal frameshifting (−1 PRF) to generate a frameshifted, C-terminally unique protein. The first experimentally verified occurrence of functionally utilized non-retroelement derived −1 PRF in humans has been reported in the mRNA encoding the immune-functioning C-C chemokine receptor 5 (CCR5). Here, we show that frameshifting does not occur during CCR5 decoding. Apart from its importance in understanding expression of a gene relevant to cancer, an HIV-1 receptor (and the associated claimed rationale for generating the first humans derived from genetically modified embryos), the findings imply that caution is appropriate in assessing results from translational reporter assays.
~and~
“Intersection between RNA methylation and TDP43-mediated toxicity in ALS”

Mike McMillan
Ph.D. candidate
Cellular and Molecular Biology
University of Michigan

Keywords: TDP43, m6A, ALS, RNA stability
Abstract: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease resulting in the death of upper and lower motor neurons. ALS has no known cure and limited therapeutic options, and the underlying pathological mechanisms remain unclear. Despite considerable variability in clinical presentation, over 95% of ALS cases exhibit cytoplasmic inclusions of the RNA binding protein TDP43. Emerging evidence suggests that TDP43 is crucial for RNA stability, and that dysregulation of RNA homeostasis may contribute to ALS pathogenesis.
Methylation of RNA at the 6th position nitrogen (N6-methyladenosine methylation, or m6A) by methyltransferases (writers) or removal of methyl groups by demethylases (erasers) has dramatic effects on RNA stability and translation mediated by a family of RNA biding proteins that recognize methylated RNA (readers). m6A writers and erasers specifically localize to nuclear speckles, membraneless nuclear organelles rich in RNA binding proteins and splicing factors, including TDP43. Together with our data showing that TDP43 regulates RNA stability, these observations suggest that TDP43 may destabilize m6A modified RNA. Here, we show that methylated RNA co-purified with TDP43 from cultured cells via RNA immunoprecipitation, and abrogation of methylation sites disrupted TDP43 binding, suggesting that TDP43 recognizes m6A modified RNA in cellulo. We also noted profound and widespread hypermethylation of coding and non-coding transcripts in ALS spinal cord, many overlapping with confirmed TDP43 target transcripts. Consistent with a central role for m6A modification in TDP43-mediated toxicity, we identified several factors operating within the m6A pathway that enhance or suppress the toxicity of TDP43 in rodent primary cortical neurons via a single-cell CRISPR/Cas9 candidate-based screen. Genetic knockout of the established m6A reader YTHDF2 rescued TDP43 toxicity in primary neurons, and YTHDF2 was also upregulated in ALS postmortem sections. Together, these data imply a fundamental link between m6A RNA modifications and ALS pathogenesis, potentially mediated by TDP43-dependent RNA destabilization.

RNA Collaborative Seminar Series // Host: European Molecular Biology Laboratory (EMBL)
2021-06-02 16:00 - 17:00
For the seminar details, visit: https://www.rnasociety.org/rna-collaborative-seminar-series

26th Annual RNA Society Virtual meeting
2021-05-25 - 2021-06-05
For more details, visit: https://www2.rnasociety.org/conferences/rna-2021/
2021 ORGANIZERS:
Gene Yeo – University of California San Diego, USA
Jörg Vogel – University of Würzburg, Germany
Katrin Karbstein – Scripps Research Institute, Florida, USA
Xavier Roca – Nanyang Technological University, Singapore
V. Narry Kim – Seoul National University, South Korea
Anna Marie Pyle – Yale University, USA

RNA Collaborative Seminar Series // Host: Groupe de Recherche RNA (GDR)
2021-05-19 09:00 - 10:00

Seminar: Nick Ingolia, UC Berkeley
2021-05-18 16:00 - 17:00
ZOOM LINK
“Dissecting gene regulatory networks with CiBER-Seq”
Nicholas Ingolia, PhD
Assistant Professor
Department of Molecular & Cell Biology
University of California, Berkeley
Faculty host:
Kristin Koutmou, Ph.D.
Seyhan N. Ege Assistant Professor of Chemistry
Department of Chemistry
Department of Chemistry Seminar
ABSTRACT: Cells integrate environmental signals and internal physiology to dynamically control gene expression. We have developed a technique to dissect this regulatory logic by linking targeted, genome-wide genetic perturbations with a deep-sequencing readout that quantitatively measures the expression phenotype induced by each perturbation. Our approach combines CRISPR interference (CRISPRi) with barcoded expression reporters (CiBER-seq) to profile transcriptional, translational, and posttranslational regulatory responses, connecting each guide in a genome-scale library with its individual phenotypic consequences. Applying CiBER-Seq to the well-studied integrated stress response (ISR) pathway recapitulated the known biology of this pathway and uncovered further triggers for ISR activation that were not previously appreciated. The quantitative phenotypic measurements from CiBER-Seq are well suited to epistasis analysis, and we measure dual-perturbation phenotypes and compare patterns of genetic interaction to gain further insight into regulatory pathways. CiBER-Seq is an incisive tool for dissecting genetic networks, and can be applied to study a wide range of biological processes, using gene expression regulation as a sensitive and specific readout of the state of the cell.

RNA Innovation Seminar: Thomas Martinez, Salk Institute for Biological Studies
2021-05-17 16:00 - 17:00
“Annotation and Characterization of Human Protein-coding Small Open Reading Frames”
Thomas Martinez, Ph.D.
Postdoctoral Fellow
Salk Institute for Biological Studies
ZOOM
REGISTRATION REQUIRED:
https://umich.zoom.us/webinar/register/WN_90RkcQTGQZa7ifQ8kbSdNQ
FLYER IN PDF
KEYWORDS: microprotein, smORF, ribosome profiling
ABSTRACT: Functional protein-coding small open reading frames (smORFs) are emerging as an important class of genes. Several smORF-encoded microproteins have been characterized and implicated in a variety of critical processes, including regulation of mRNA decay, DNA repair, and muscle formation. Thus, rigorous and comprehensive annotation of protein-coding smORFs is critical to our understanding of basic biology and physiology, as well as disease. We recently developed an improved workflow that integrates de novo transcriptome assembly and ribosome profiling to overcome obstacles with previous methods to more confidently annotate thousands of novel smORFs across multiple human cell lines, including hundreds encoded on putative non-coding RNAs. Over 1,500 smORFs are found in two or more cell lines, and ~40% lack a canonical AUG start codon. Evolutionary conservation analyses suggest that hundreds of smORF-encoded microproteins are likely functional. We also find that smORF-derived peptides are detectable on human leukocyte antigen complexes, positioning smORFs as a source of novel antigens. The annotation of protein-coding smORFs radically alters the current view of the human genome’s coding capacity and will provide a rich pool of unexplored, functional human genes.
BIOGRAPHY: Thomas received his B.S. in Biological Engineering from MIT and trained in Prof. JoAnne Stubbe’s laboratory, where he studied the mechanism of ribonucleotide reductase. He then received his Ph.D. in Biochemistry & Molecular Biophysics from Caltech as an NIH NRSA predoctoral fellow under the mentorship of Prof. Peter Dervan. His thesis work focused primarily on characterizing the effects of DNA binding pyrrole-imidazole polyamides on DNA replication in prostate cancer cells. Thomas is currently an NIH NRSA postdoctoral fellow in Prof. Alan Saghatelian’s laboratory, where he has developed an integrative platform combining ribosome profiling and de novo transcriptome assembly to discover functional smORF encoded microproteins in the human genome.

RNA Collaborative Seminar Series // Host: Cambridge RNA Club
2021-05-05 09:00 - 10:00

Seminar: Tatjana Trcek, Johns Hopkins University
2021-05-04 15:00 - 16:00
Zoom link
“RNA Granules: A View from the RNA Perspective”
Tatjana Trcek, PhD
Assistant Professor
Department of Biology
Johns Hopkins University

Hosted by:
Stephanie Moon, Ph.D.
Assistant Professor of Human Genetics
Faculty Scholar of the Center for RNA Biomedicine
Affiliate Faculty, Biological Chemistry
FLYER IN PDF
Department of Human Genetics Seminar

RNA Innovation Seminar: Olivia Rissland, University of Colorado School of Medicine
2021-05-03 16:00 - 17:00
“Regulating the Regulators: Control of RNA Binding Proteins during Embryogenesis”
Olivia Rissland, Ph.D.
Assistant Professor
RNA Bioscience Initiative | Department of Biochemistry & Molecular Genetics
University of Colorado School of Medicine
ZOOM
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FLYER IN PDF

ABSTRACT: The maternal-to-zygotic transition (MZT) is a conserved step in animal development, where control is passed from the maternal to the zygotic genome. Although the MZT is typically considered from its impact on the transcriptome, we previously found that three maternally deposited Drosophila RNA binding proteins (ME31B, Trailer Hitch [TRAL], and Cup) are also cleared during the MZT by unknown mechanisms. Here, we show that these proteins are degraded by the ubiquitin-proteasome system. Marie Kondo, an E2 conjugating enzyme, and the E3 CTLH ligase are required for the destruction of ME31B, TRAL, and Cup. Structure modeling of the Drosophila CTLH complex suggests that substrate recognition is different than orthologous complexes. Despite occurring hours earlier, egg activation mediates clearance of these proteins through the Pan Gu kinase, which stimulates translation of Kondo mRNA. Clearance of the maternal protein dowry thus appears to be a coordinated, but as-yet underappreciated, aspect of the MZT.

RNA Collaborative Seminar Series // Host: Shanghai RNA Club
2021-04-21 09:00 - 10:00

RNA Innovation Seminar: Jailson (Jay) Brito Querido, MRC Laboratory of Molecular Biology
2021-04-19 16:00 - 17:00
“Structural insights into mRNA translation initiation in humans”
Jailson (Jay) Brito Querido, Ph.D.
Postdoctoral Scientist
MRC Laboratory of Molecular Biology
Cambridge, UK
ZOOM
FLYER IN PDF
REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_78YYOhIhTbOBy2_JSdM7Wg
ABSTRACT: A key step in translational initiation is the recruitment of the 43S pre-initiation complex (43S PIC) by the cap-binding complex (eIF4F) at the 5´ end of mRNA. Eukaryotic initiation factors eIF1, eIF1A, eIF3, eIF5, and the ternary complex (TC) of eIF2–GTP–tRNAiMet bind to the 40S ribosomal subunit to form the 43S PIC. Once assembled, the 43S PIC is recruited to the cap-binding complex eIF4F at the 5´end of mRNA to form a 48S initiation complex (48S). The 48S then scans along the mRNA to locate a start codon. To understand the mechanisms involved, we determined the structure of a reconstituted human 48S using cryo-electron microscopy. The structure reveals insights into early events of translation initiation complex assembly. It reveals how eIF4F interacts with subunits of the eIF3 structural core near the mRNA exit channel in the 43S. The location of eIF4F is consistent with a slotting model of mRNA recruitment and suggests a “blind-region” that would preclude recognition of start sites upstream of the location of the P site at the point of recruitment.
KEYWORDS: mRNA, ribosome, eIF4F, eIF4A, translation

Stephanie Moon, Ph.D., "RNA regulation in proteotoxic stress and genetic neurological disorders"
2021-04-13 16:00 - 17:00
“RNA regulation in proteotoxic stress and genetic neurological disorders”

Stephanie Moon, PhD
Assistant Professor of Human Genetics, a Faculty Scholar of the Center for RNA Biomedicine, and an Affiliate Faculty of Biological Chemistry at the University of Michigan
Faculty Host: Sundeep Kalantry, PhD, Associate Professor of Human Genetics
Zoom link: https://umich-health.zoom.us/j/92442599246
FLYER IN PDF
Center for Cell Plasticity and Organ Design Seminar

RNA Collaborative Seminar Series // Host: Bay Area RNA Club (BARC)
2021-04-07 16:00 - 17:00

Seminar: Eva Nogales, Ludwig Lecture
2021-04-06 12:00 - 13:00
“Exploring the Modularity of Large Complexes Involved in Transcription Initiation and Chromatin Modifications”

Eva Nogales, PhD
Howard Hughes Medical Institute investigator, Professor of Biochemistry and Molecular Biology
University of California, Berkeley
Senior Faculty Scientist
Lawrence Berkeley National Laboratory

Department of Biological Chemistry, Ludwig Lecture

RNA Innovation Seminar: Natoya Peart, University of Pennsylvania
2021-04-05 16:00 - 17:00
“Direct binding of ESRP1 to regulated transcripts is required for position-dependent splicing regulation”
Natoya Peart, Ph.D.
Postdoctoral Researcher – Carstens Lab/Lynch Lab
Department of Medicine/Department of Biochemistry and Molecular Biophysics
University of Pennsylvania
ZOOM
REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_0lUfePb0Qdac-cQZDpeiEQ
FLYER IN PDF
KEYWORDS: Alternative splicing, RNAMap, Esrp1
ABSTRACT: Coordinated regulation of alternative splicing is essential to the establishment of cell identity. The Epithelial Splicing Regulatory Proteins (Esrps), ESRP1 and ESRP2, are highly conserved paralogous proteins required for organogenesis of multiple organ systems and compromised function of Esrps contributes to human diseases and pathologies. Esrps are robustly expressed in the epithelial cells of the epidermis, large and small intestines, salivary glands, stomach, and a variety of other tissues, where they are vital in promoting an epithelial splicing network. Although ESRP1 and ESRP2 share partial functional redundancy, ESRP1 appears to play a larger role in regulating gene expression.
Using a combination of enhanced immunoprecipitation coupled with high throughput sequencing (eCLIP) in the epithelial cells of mouse epidermis and RNA sequencing analysis of alterations in splicing and total gene expression that result from epidermal ablation of Esrp1 and Esrp2 we generate a map of Esrp1 binding to RNA. We show that ESRP1 regulates splicing primarily through direct binding in a position-dependent manner to either promote exon inclusion or skipping. In particular, we show that Esrp1 binding upstream of or withing alternatively spliced exons suppresses exon inclusion, whilst binding downstream of the non-constitutive exon promotes exon inclusion. In addition, we identified widespread binding of ESRP1 in 3’ and 5’ untranslated regions (UTRs) of genes enriched for epithelial cell function suggesting that it directly regulates post-transcriptional gene expression steps in addition to splicing.

5th Annual RNA Symposium: "Processing RNA" - Day 2
2021-03-26 11:00 - 14:30
Day 2
11:00–11:05 / Welcome
11:05–12:00 / Keynote 4: Brenda Bass, Ph.D., University of Utah (RNA editing & silencing)
12:00–12:10 / Short break
12:10–1:05 / Keynote 5: Christopher Lima, Ph.D., Memorial Sloan-Kettering (RNA degradation)
1:05–1:35 / Data Blitz (three finalists from the poster submissions)
1:35–2:25 / Panel discussion with keynote speakers
2:25–2:30 / Closing
REGISTRATION REQUIRED
View full schedule here

5th Annual RNA Symposium: "Processing RNA" - Day 1
2021-03-25 11:00 - 14:30
Day 1
11:00–11:05 / Welcome
11:05–12:00 / Keynote 1: Tracy Johnson, Ph.D., University of California – Los Angeles (RNA splicing)
12:00–12:10 / Short break
12:10–1:05 / Keynote 2: Kevin Weeks, Ph.D., University of North Carolina (RNA structure in vivo)
1:05–1:35 / Data Blitz (three finalists from the poster submissions)
1:35–2:30 / Keynote 3: Feng Zhang, Ph.D., MIT (CRISPR applications)
2:30–2:30 / Brief closing
REGISTRATION REQUIRED
View full schedule here

RNA Collaborative Seminar Series // Host: UMass Medical School, RNA Therapeutics Institute
2021-03-24 16:00 - 17:00

RNA Innovation Seminar: James Nuñez, HHMI Hanna Gray Fellow, UCSF
2021-03-15 16:00 - 17:00
“Programmable transcriptional memory by CRISPR-based epigenome editing”
James Nuñez, Ph.D.
HHMI Hanna Gray Fellow
University of California, San Francisco
ZOOM
REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_hZw_8jjWQo-7goOvohXOPg
FLYER IN PDF

ABSTRACT: General approaches for heritably altering gene expression would enable many discovery and therapeutic efforts. I will present CRISPRoff— a programmable epigenetic memory writer consisting of a single dead Cas9 fusion protein that establishes DNA methylation and repressive histone modifications to turn off transcription. Transient CRISPRoff expression initiates highly specific DNA methylation and gene repression that is maintained through cell division and differentiation of stem cells to neurons. Pairing CRISPRoff with genome-wide screens and analysis of chromatin marks enabled us to explore the rules for heritable silencing. We identify sgRNAs capable of silencing the large majority of genes including those lacking canonical CpG islands (CGIs) and reveal a wide targeting window extending beyond annotated CGIs. Our finding that targeted DNA methylation outside of CGIs leads to memorized gene silencing expands the canonical model of methylation-based silencing and broadly enables diverse applications including genome-wide screens, multiplexed cell engineering, enhancer silencing, and mechanistic exploration of epigenetic inheritance.
KEYWORDS: CRISPR, transcription, epigenetics

RNA Collaborative Seminar Series // Host: Alberta RNA Research and Training Institute (ARRTI)
2021-03-10 16:00 - 17:00

BiolChem Seminar: Lori Passmore, MRC Laboratory of Molecular Biology
2021-03-09 12:00 - 13:00
“Mechanistic Insights into the mRNA Poly(A) Tail Machinery”

Lori Passmore, Ph.D.
MRC Laboratory of Molecular Biology

Department of Biological Chemistry, Greenberg Lecture

RNA Innovation Seminar: Melissa J. Moore - Chief Scientific Officer, Moderna Therapeutics
2021-03-03 16:00 - 17:00
This event was rescheduled from February 10, 4:00 pm.
To attend on March 3rd, please register again. Apologies for the inconvenience.
ZOOM REGISTRATION REQUIRED
“A timely confluence: The backstory of Moderna’s COVID-19 vaccine”

Melissa Moore, Ph.D.,
Chief Scientific Officer, Moderna Therapeutics
Dr. Moore will address scientists and non-scientists, and will take live questions.
FLYER IN PDF
In her role as Chief Scientific Officer, Platform Research, Dr. Melissa Moore is responsible for leading mRNA biology, delivery and computation science research at Moderna. She joined Moderna in 2016 from the University of Massachusetts Medical School, where she served as Professor of Biochemistry & Molecular Pharmacology, Eleanor Eustis Farrington Chair in Cancer Research and a long-time Investigator at the Howard Hughes Medical Institute (HHMI). Dr. Moore was also a founding Co-Director of the RNA Therapeutics Institute (RTI) at UMassMed, and was instrumental in creating the Massachusetts Therapeutic and Entrepreneurship Realization initiative (MassTERi), a faculty-led program intended to facilitate the translation of UMMS discoveries into drugs, products, technologies and companies. Dr. Moore is an elected member of the National Academy of Sciences (2017) and a Fellow of the American Academy of Arts and Sciences (2019).
Dr. 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 began working on RNA metabolism during her postdoctoral training with Phillip A. Sharp at MIT. During her 23 years as a faculty member, first at Brandeis and then at UMassMed, 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.

RNA Collaborative Seminar Series // Host: Helmholtz Institute for RNA-based Infection Research
2021-02-24 09:00 - 10:00
Presenters:
Neva Caliskan, Ph.D.
Mathias Munschauer, Ph.D.
For the seminar details, visit: https://www.rnasociety.org/rna-collaborative-seminar-series

BiolChem Seminar: Katrin Karbstein, Scripps Institute Florida
2021-02-23 12:00 - 13:00
“Choreographing Ribosome Assembly”

Katrin Karbstein, Ph.D.
Scripps Institute Florida

Department of Biological Chemistry, Greenberg Lecture
Zoom link: https://umich.zoom.us/j/96151442305

RNA Innovation Seminar: Karla Neugebauer, Yale University
2021-02-15 16:00 - 17:00
“Dynamics of co-transcriptional pre-mRNA processing and assembly of related biomolecular condensates”
Prof. Karla Neugebauer, Ph.D.
Professor of Molecular Biophysics and Biochemistry and of Cell Biology
Director of Graduate Studies, Molecular Biophysics and Biochemistry
Director, Yale Center for RNA Science and Medicine
Yale School of Medicine
ZOOM
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FLYER IN PDF
Abstract: My lab is interested in the coordination between transcription, RNA processing and nuclear organization that governs gene expression. We have established experimental systems in budding yeast, zebrafish embryos, and mammalian tissue culture cells to explore transcription and splicing regulation in a variety of biological contexts and with a diversity of tools, from imaging to genome-wide approaches. Our observations have provided novel insights into transcription and splicing mechanisms as well as principles of cellular organization that facilitate efficient gene expression. In this talk, I will be discussing rapid co-transcriptional splicing during erythropoiesis and how Cajal bodies assemble to ensure a steady supply of spliceosomal components.

LSI Seminar: Blanton S. Tolbert, Ph.D., Case Western Reserve University
2021-02-04 12:00 - 13:00
Structural biophysics of RNA interactions that contribute to viral replication
Blanton S. Tolbert, Ph.D.
Professor of Chemistry
Case Western Reserve University

LSI Seminar Series
Interests: Biochemistry, Biophysical Chemistry, Structural Biology
Blanton S. Tolbert is a professor of chemistry at Case Western Reserve University, where he oversees a diverse research group that endeavors to understand biochemical mechanisms by which human pathogenic RNA viruses replicate within cells, and to leverage this knowledge to identify novel drug targets for therapeutic intervention. Tolbert is the PI of multiple NIH grants, and he has published in top journals including Nature Communications, the Proceedings of the National Academy of Sciences and the Journal of the American Chemical Society. Tolbert also serves on the NIH Office of AIDS Research Advisory Council (OARAC), and he will become the next chair of OARAC in 2021. He is a member of the Burroughs Wellcome Fund Postdoctoral Enrichment Program Advisory Board and an editor for the Journal of Biological Chemistry and Microbiology and Molecular Biology Reviews. Tolbert is the proud father of two boys, and in his spare time he enjoys exploring the outdoors in the Cleveland Metroparks.

RNA Innovation Seminar: Jeff Twiss, University of South Carolina
2021-02-01 16:00 - 17:00 | Virtual
“Regulating the axonal proteome through mRNA transport and translation”

Jeffrey L. Twiss, M.D., Ph.D.
SmartState Chair in Childhood Neurotherapeutics
Professor of Biological Sciences
University of South Carolina

ZOOM
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FLYER IN PDF
Abstract: Neurons are extremely polarized cells with axonal and dendritic processes extending 100 to 1000 fold longer or more than the cell body diameter. Our lab has been interested in how axons grow to such great distances and how they respond to injury. mRNAs are transported into axons, with their localized translation providing the axon with autonomy to respond to different stimuli by modifying their local proteome. Transport, translation, and stability of axonal mRNAs is driven by interactions with RNA binding proteins and different signaling cascades. I will focus on recent work that gives insight into how specificity of these mechanisms is driven for different cohorts of axonal mRNAs.
Keywords: Neuron, Axon, RNA transport, Translational regulation

RNA Innovation Seminar: Elena Conti, Max Planck Institute of Biochemistry
2021-01-25 09:00 - 10:00
Talk title: The RNA exosome complex: the Dr Jekyll and Mr Hyde of RNA degradation
Elena Conti, PhD
Director, Max Planck Institute of Biochemistry

ZOOM
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Flyer in PDF
Keywords: molecular mechanisms, RNA, ribosome, biochemistry, cryo-EM, X-ray crystallography
Abstract: All RNAs in eukaryotic cells are eventually degraded. The RNA exosome is a conserved macromolecular machine that degrades a vast number and variety of RNAs. Exosome-mediated RNA degradation leads to the complete elimination of nuclear and cytoplasmic transcripts in turnover and quality control pathways, and to the partial trimming of RNA precursors in nuclear processing pathways. How the exosome combines specificity and versatility to either eliminate or process RNAs has been a long-standing question.
Over the years, our group has used biochemical and structural approaches to understand how the exosome core complex channels RNA substrates for degradation and how it associates with its nuclear and cytoplasmic cofactors. Visualizing how the exosome cofactors interact with pre-ribosomes in the nucleus and with mature ribosomes in the cytoplasm has provided insights into the mechanisms with which different exosome-ribosome assemblies underpin opposite outcomes of RNA degradation: a constructive function of the nuclear exosome in the maturation of the large ribosomal subunit and a destructive function of the cytoplasmic exosome in the destruction of ribosome-bound mRNAs. Ongoing work is uncovering the unanticipated levels of regulation intrinsic to this multi-purpose degradation machinery.
Our group has a long-standing interest in RNA metabolism, with a particular focus on the molecular mechanisms of eukaryotic RNA transport and degradation. >more

RNA Collaborative Seminar Series - NCI RNA Biology Initiative hosting
2021-01-13 16:00 - 17:00

RNA Collaborative Seminar Series - European Molecular Biology Laboratory (EMBL) hosting
2020-12-16 09:00 - 10:00
