Center for RNA Biomedicine

RNA Collaborative Seminar Series // Host: University of Michigan
2021-06-30 16:00 - 17:00 (America/Detroit)
REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_6OEQ6sDAQ0-21GHm6d7VEQ

“Dynamic multivalent interactions drive mammalian RNA regulation”

Sethu Pitchiaya, Ph.D.
Department of Urology

“Characterizing cellular RNA-protein interaction networks with chemical probes”
Chase Weidmann, Ph.D.
Department of Biological Chemistry

For the seminar details, visit: https://www.rnasociety.org/rna-collaborative-seminar-series

RNA Collaborative Seminar Series // Host: iRNA @ Istituto Italiano di Tecnologia (IIT)
2021-07-14 09:00 - 10:00
For the seminar details, visit: https://www.rnasociety.org/rna-collaborative-seminar-series

RNA Collaborative Seminar Series // Host: MD Anderson Center for RNA Interference and Non-Coding RNAs
2021-07-28 09:00 - 10:00

RNA Collaborative Seminar Series // Host: RiboClub Sherbrooke
2021-08-11 16:00 - 17:00

RNA Collaborative Seminar Series // Host: Institute of Molecular Biology (IMB)
2021-08-25 09:00 - 10:00

RNA Innovation Seminar: Byron Purse, Ph.D.
2021-10-04 16:00 - 17:00
“Fluorescent nucleoside analogues with new properties”
Byron Purse, Ph.D.
Associate Professor
Organic Chemistry
San Diego State University

HYBRID SEMINAR:
In-person: Forum Hall, Palmer Commons
Zoom: https://umich.zoom.us/webinar/register/WN__vvE2dtHQi-R3h05JUHBzQ
FLYER IN PDF
Abstract:
Fluorescent nucleoside analogues (FNAs) are powerful probes for studying the structure and dynamics of nucleic acids, which are vital to understanding RNA function, DNA damage repair, nucleic acid–protein interactions, regulatory mechanisms for gene expression, and other aspects of nucleic acid function. Existing FNAs are prone to quenching by base pairing and stacking, are clustered at the blue–green end of the visible spectrum, and have limited brightness as compared with conventional fluorophores. Studies of nucleic acid function would benefit greatly from overcoming these limitations. We have designed, synthesized, and studied a series of fluorescent pyrimidine analogues, aiming to address these limitations and develop a detailed understanding of the relationships between chemical structure and fluorescent responses to local environment in nucleic acids. Included in this series is a tricyclic cytidine analogue DEAtC that is nearly non-fluorescent as a nucleoside, but responds to matched base pairing and stacking with a fluorescence turn-on. A chlorinated tricyclic cytidine 8-Cl-tCO reports on local environment by changes in the vibrational fine structure of its emission spectra. To address the problem of limited brightness, we have design and synthesized a new NFA that we call ABN, which has a conjugated push–pull system similar to those found in bright fluorophores such as rhodamines. ABN is the brightest known FNA when present in duplex nucleic acids, and it is readily detected in single-molecule fluorescence measurements using both 1-photon and 2-photon excitation. Collectively, these FNAs offer new capabilities for biophysical studies on nucleic acids. Comparisons of their structure and properties help to reveal mechanisms for fluorescence changes in response to local environment in nucleic acids.

Human Genetics Seminar: Rajesh Rao, Ophthalmology & Visual Science, U-M Medical School
2021-10-05 15:00 - 16:00
“Genetics through the Lens of an Ophthalmologist and Vision Scientist”
Rajesh C. Rao, M.D.
Leonard G. Miller Professor
Associate Professor
Department of Ophthalmology & Visual Sciences
Department of Pathology

Department of Human Genetics seminar
ZOOM MEETING ID: 947 5800 7294
PASSCODE: [REDACTED]
https://umich.zoom.us/j/94758007294?pwd=[REDACTED]
FLYER IN PDF

RNA Innovation Seminar: Tim Stasevich, Ph.D.
2021-10-18 16:00 - 17:00
“Imaging single-mRNA translation dynamics in living color”
Tim Stasevich, Ph.D.
Associate Professor
Dean and Pingping Tsao Professor of Biochemistry
CSU Monfort Professor
Boettcher Investigator
Colorado State University
Registration: https://umich.zoom.us/webinar/register/WN_OzTuwf2zRN-6zCZk1pA_lQ

Flyer in PDF
Keywords:
translational regulation, gene expression, fluorescence microscopy, intrabodies, single-molecule imaging
Abstract:
My lab is creating technology to image mRNA translation in real time and with single-molecule precision in living cells. In this talk, I will introduce our technology and describe how it can be used to amplify fluorescence from newly synthesized proteins as they are being translated from single mRNAs. I will show how we quantify these signals to determine the size, shape, subcellular localization, and mobilities of mRNA translation sites, as well as their protein synthesis dynamics. I will then highlight a few recent applications of our technology, focusing mainly on a new biosensor we have developed to quantify how individual regulatory factors impact single mRNA translation dynamics. Using this biosensor, we provide evidence that human Argonaute2 (Ago2) shuts down translation by down regulating translation initiation on the minutes timescale and helping usher translationally silent mRNAs into P-bodies on the hours timescale. I will conclude by discussing new fluorescent intrabodies my lab is engineering to light up nascent and mature proteins in multiple colors. As these intrabodies can be encoded on plasmids, they can easily be adapted by other labs to image gene activity in diverse living systems.
Timothy J. Stasevich is an Associate Professor in the Department of Biochemistry and Molecular Biology at Colorado State University (CSU). His lab uses a combination of advanced fluorescence microscopy, genetic engineering, and computational modeling to study the dynamics of gene regulation in living mammalian cells. His lab helped pioneer the imaging of real-time single-mRNA translation dynamics in living cells1. Dr. Stasevich received his B.S. in Physics and Mathematics from the University of Michigan, Dearborn, and his Ph. D. in Physics from the University of Maryland, College Park. He transitioned into experimental biophysics as a post-doctoral research fellow in the laboratory of Dr. James G. McNally at the National Cancer Institute. During this time, he developed technology based on fluorescence microscopy to help establish gold-standard measurements of live-cell protein dynamics. Dr. Stasevich next moved to Osaka University, where he worked with Dr. Hiroshi Kimura as a Japan Society for the Promotion of Science Foreign Postdoctoral Research Fellow. While there, he helped create technology to image endogenous proteins and their post-translation modifications in vivo. This allowed him to image the live-cell dynamics of epigenetic histone modifications during gene activation for the first time2. Before joining the faculty at CSU, Dr. Stasevich spent a year as a Visiting Fellow at the HHMI Janelia Research Campus, where he applied superresolution fluorescence microscopy to improve the spatiotemporal resolution of endogenous protein imaging in live cells.
1. Morisaki, T. et al. Real-time quantification of single RNA translation dynamics in living cells. Science 352, 1425–1429 (2016).
2. Stasevich, T. J. et al. Regulation of RNA polymerase II activation by histone acetylation in single living cells. Nature 516, 272–275 (2014).

RNA Innovation Seminar: Zhonggang Hou & Jun Hee Lee
2021-11-08 16:00 - 17:00
“Harnessing diverse compact CRISPR-Cas3 for long-range genome engineering”
Zhonggang Hou, Ph.D.
Research Investigator
Biological Chemistry
ABSTRACT: Leading CRISPR-Cas technologies employ Cas9 and Cas12 enzymes that generate RNA-guided dsDNA breaks. Yet, the most abundant microbial adaptive immune systems, Type I CRISPR, is under-exploited for eukaryotic application. I will discuss our effort on adopting the first minimal CRISPR-Cas3 from Neisseria Type I-C system, to create targeted large chromosomal deletions in human cells. RNP delivery of the processive Cas3 nuclease and target recognition complex Cascade, gave up to 90% editing efficiency. Unexpectedly, Type I-C Cascade assembly in bacteria requires a previous unknown internal translation product Cas11 from within the cas8 gene. Our data show that expression of a separately encoded Cas11 is the key to enable plasmid- and mRNA- based editing in human cells. We demonstrate that “supplying cas11” is a universal strategy to harness divergent and streamlined Type I-C, I-D and I-B editors with distinct PAM preferences and guide orthogonality. Our findings expand the CRISPR toolbox for long-range genome engineering.
KEYWORDS: CRISPR; genome editing; Cascade; Cas3; Cas11; DNA targeting; crRNA; large deletion; Neisseria; genome engineering

“Microscopic Examination of Spatial Transcriptome through Seq-Scope”
Jun Hee Lee, Ph.D.
Associate Professor
Molecular & Integrative Physiology
KEYWORDS: Spatial Transcriptomics, Seq-Scope

Registration: https://umich.zoom.us/webinar/register/WN_qBK6mw7vQa6jOkZuS81_VQ
FLYER IN PDF

RNA Faculty Candidate Seminar: Paul Donlin-Asp, Max Planck Institute for Brain Research
2021-12-13 16:00 - 17:00
“Resolving the localisation and dynamics of mRNA and protein synthesis within neurons”
Paul Donlin-Asp, Ph.D.
Postdoctoral Researcher
Department of Synaptic Plasticity
Max Planck Institute for Brain Research

Flyer in PDF
Co-Host: The Department of Molecular, Cellular, and Developmental Biology
Hybrid Seminar:
In-person: Biomedical Science Research Building (BSRB), ABC Seminar rooms
Zoom: https://umich.zoom.us/webinar/register/WN_tZjYxppSQwaDVTYIuC0jkw
Keywords: mRNA dynamics, local protein synthesis, neurons, neuronal cell biology, synaptic plasticity, in vivo imaging
In-person event COVID guidelines

RNA Faculty Candidate Seminar: Dr. Alisha 'Jonesy' Jones, Institute of Structural Biology, Helmholtz Zentrum Munich
2021-12-20 16:00 - 17:00
“Modulation of the MALT1 pre-mRNA structure by hnRNP proteins regulates T cell activation”
Dr. Alisha ‘Jonesy’ Jones
Postdoctoral Researcher
Institute of Structural Biology
Helmholtz Zentrum Munich

Flyer in PDF
Co-Hosts: The Center for RNA Biomedicine, Department of Biological Chemistry, and the Program in Biophysics
Hybrid Seminar:
In-person: Biomedical Science Research Buliding (BSRB), ABC Seminar rooms
Zoom: https://umich.zoom.us/webinar/register/WN_3yrQ47UuTKKuzigbe38Sww
Keywords: pre-mRNA, hnRNP, NMR, SHAPE, structure
Abstract: 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.
In-person event COVID guidelines

RNA Faculty Candidate Seminar: Rachel Niederer, Yale School of Medicine
2022-01-10 16:00 - 17:00
“Uncovering novel translational control elements within 5′ UTRs”
Rachel Niederer, Ph.D.
Postdoctoral Researcher
Yale School of Medicine

Co-Hosts: The Center for RNA Biomedicine, Department of Biological Chemistry, and the Department of Human Genetics
Hybrid Seminar:
In-person: Biomedical Science Research Buliding (BSRB), ABC Seminar rooms
Zoom: https://umich.zoom.us/webinar/register/WN_qg4fyCUbQZyVu0oGrBLmWQ
Abstract: 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.
In-person event COVID guidelines
Flyer in PDF

RNA Faculty Candidate Seminar: Jailson (Jay) Brito Querido, MRC Laboratory of Molecular Biology
2022-01-31 16:00 - 17:00
“The scanning mechanism of mRNA translation initiation in humans”
Jailson (Jay) Brito Querido, Ph.D.
Postdoctoral Scientist
MRC Laboratory of Molecular Biology
Cambridge, UK

Co-Hosts: The Center for RNA Biomedicine, Department of Biological Chemistry, and the Program in Biophysics
Hybrid Seminar:
In-person: Biomedical Science Research Building (BSRB), ABC Seminar rooms
Zoom: https://umich.zoom.us/webinar/register/WN_pcS-fWIdSS-hDnKzoRhXeg
Keywords: mRNA, translation, ribosome, helicase
Abstract: 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.
In-person COVID Events Policy

RNA Faculty Candidate Seminar: Margaret (Maggie) Rodgers, Johns Hopkins University
2022-02-14 16:00 - 17:00
“Mechanisms of co-transcriptional ribonucleoprotein assembly”
Margaret (Maggie) Rodgers, Ph.D.
Postdoctoral Researcher
Johns Hopkins University

Co-Hosts: The Center for RNA Biomedicine, Department of Biological Chemistry, and the Program in Biophysics
Hybrid Seminar:
In-person: Biomedical Science Research Buliding (BSRB), ABC Seminar rooms
Zoom: https://umich.zoom.us/webinar/register/WN_Icqg8jRbQNGCBEFkj_u5Gw
Keywords: RNA, RNP, ribosome assembly, transcription, single-molecule fluorescence
Seminar flyer in PDF
In-person event COVID guidelines

Seminar: John Prensner, MD, PhD
2022-02-28 16:00 - 17:00
“Translating the cancer genome: dark matter proteins”
John Prensner, M.D., Ph.D.
Physician, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center
Instructor of Pediatrics, Harvard Medical School

Co-Hosts: The Center for RNA Biomedicine, Department of Computational Medicine & Bioinformatics, and Department of Pediatric Oncology
Hybrid Seminar:
In-person: Biomedical Science Research Building (BSRB), ABC Seminar rooms
Zoom: https://umich.zoom.us/webinar/register/WN_bC6oy6VZTLy3ke4iMS2sKQ
Keywords: cancer, ribosome profiling, functional genomics, gene discovery
Abstract: 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.
In-person COVID Events Policy

RNA Therapeutics Seminar, Michelle Hastings, Rosalind Franklin University
2022-03-21 15:00 - 16:00
Inaugural RNA Therapeutics Seminar
Michelle Hastings, Ph.D.
Professor, Cell Biology and Anatomy; Director, Center for Genetic Diseases
Rosalind Franklin University of Medicine and Science

This is an internal U-M event:
In-person: Palmer Commons, Forum Hall
Zoom: https://umich.zoom.us/webinar/register/WN_mUj40sudTwmI6hXANnlJEg
Keywords: pre-mRNA splicing, Antisense oligonucleotides, Usher syndrome, Batten Disease, lysosomal storage diseases
Seminar flyer in PDF
In-person COVID Events Policy

RNA Innovation Seminar: Sika Zheng, UC Riverside, School of Medicine
2022-05-09 16:00 - 17:00
“Unexpected determinants of neuronal identity and properties: the curious cases of PTBP1, PTBP2, and neuronal splicing”
Sika Zheng, Ph.D.
Associate Professor, Director of Center for RNA Biology and Medicine
UC Riverside, School of Medicine

Flyer in PDF

Virtual Seminar
Zoom: https://umich.zoom.us/webinar/register/WN_dltbxWdHQ5KrC3rTl4hqLQ
Abstract:
Alternative 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.
References:
Zhang M, Ergin V, Lin L, Stork C, Chen L, Zheng S. Neuron. 2019 Feb 20;101(4):690-706.e10.
Ergin V, Zheng S. J Mol Biol. 2020 Jun 26;432(14):4154-4166.
Zheng S. Wiley Interdiscip Rev RNA. 2020 Jul;11(4):e1585.
Lin L, Zhang M, Stoilov P, Chen L, Zheng S. Neuron. 2020 Sep 23;107(6):1180-1196.e8.
Vuong J, Ergin V, Zheng S. Nature Communications (accepted)

RNA Innovation Seminar: Daniel O’Reilly
2022-05-16 16:00 - 17:00
“An Academic Approach to Oligonucleotide Therapeutics”
Daniel O’Reilly Ph.D., MRSC
Post-Doctoral Associate
Khvorova Lab
RNA Therapeutics Institute
University of Massachusetts Medical School
Flyer in PDF

HYBRID SEMINAR:
In-person: BSRC, ABC seminar rooms
Zoom: https://umich.zoom.us/webinar/register/WN_dM1a1aKVTM2KfwiieutOWg
Keywords: Oligonucleotides, Chemical Modifications, RNA, Huntington’s Disease
Abstract: 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.
Oligonucleotides 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.
In 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.

RNA Innovation Seminar: Zhipeng Lu, USC
2022-09-12 16:00 - 17:00
“RNA Structures, Interactions and Modifications”
Zhipeng Lu (鲁志鹏), Ph.D.
Assistant Professor
Pharmacology and Pharmaceutical Sciences
University of Southern California

Flyer in PDF
In-person: BSRB, ABC seminar rooms / hybrid link
Abstract: 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.

RNA Innovation Seminar: David Shechner, University of Washington
2022-09-26 16:00 - 17:00
“Meet the neighbors: A universal technology for probing RNA-interactions and RNA-scaffolded subcellular compartments in situ”
David Shechner Ph.D.
Assistant Professor of Pharmacology
University of Washington

Flyer in PDF
In-person: BSRB, ABC seminar rooms / hybrid link
Keywords: RNA, proximity-biotinylation, subcellular architecture, nuclear architecture, spatial biology, biomolecular condensates, interactomics, nucleolus, Xist.

Abstract: 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.
To 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.
Using 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.
Given 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.

RNA Innovation Seminar: Polly Hsu, Michigan State University
2022-10-10 16:00 - 17:00
“Roadblocks on mRNAs? Gene Expression Regulation by Upstream Open Reading Frames in Plants”
Polly Hsu, Ph.D.
Assistant Professor
Biochemistry and Molecular Biology
Michigan State University

Flyer in PDF
In-person: BSRB, ABC seminar rooms / hybrid link
Keywords: translation, uORFs, nonsense-mediated decay
Abstract: 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.

RNA Innovation Seminar: Joseph Yesselman, Ph.D. — University of Nebraska
2024-10-07 16:00 - 17:00 | BSRB – Kahn Auditorium
The University of Michigan Center for RNA Biomedicine Seminar Series will host Joseph Yesselman, Ph.D., as part of the 2024 – 2025 RNA Innovation Seminar Series.
Joseph Yesselman, Ph.D.
Assistant Professor, Chemistry
University of Nebraska

Date and Time: Monday, October 7 | 4 p.m.
In-person: Kahn Auditorium, BSRB
Hybrid Option: Click here to join the Zoom.

Talk Title: “High-throughput determination of RNA tertiary contact thermodynamics by quantitative DMS chemical mapping”
Abstract:
Structured RNAs often contain long-range tertiary contacts that are critical to their function. Despite the importance of tertiary contacts, methods to measure their thermodynamics are low throughput or require specialized instruments. Here, we introduce a new quantitative chemical mapping method (qMaPseq) to measure Mg2+-induced formation of tertiary contact thermodynamics in a high-throughput manner using standard biochemistry equipment. With qMaPseq, we measured the ΔG of 98 unique tetraloop/tetraloop receptor (TL/TLR) variants in a one-pot reaction. These results agree well with measurements from specialized instruments (R2=0.64). Furthermore, the DMS reactivity of the TL directly correlates to the stability of the contact (R2=0.68), the first direct evidence that a single DMS reactivity measurement reports on thermodynamics. Combined with structure prediction, DMS reactivity allowed the development of experimentally accurate 3D models of TLR mutants. These results demonstrate that qMaPseq is broadly accessible, high-throughput, and directly links DMS reactivity to thermodynamics.
Please visit the Yesselman Lab website to learn more about Dr. Yesselman and his work.

RNA Innovation Seminar: Laura Scott, Ph.D., University of Michigan School of Public Health
2024-10-21 16:00 - 17:00 | BSRB – Kahn Auditorium
“Regulation of RNA levels in muscle and adipose tissues by sex and genetic variants”
Laura Scott, Ph.D.
Research Professor, Biostatistics
University of Michigan School of Public Health
Research interests:
Dr. Scott uses a combination of bulk and single nucleus omic data – RNA expression, chromatin accessibility, metabolites and DNA methylation – to understand the cellular genetic regulatory landscape and to infer biological connections between genetic variation and disease risk.
Click here to read more about Dr. Scott and her work in a 2020 Faculty Spotlight article.
In-person: BSRB, Kahn Auditorium / hybrid link

Abstract:
Gene expression is regulated by multiple factors including genetic variation, sex, and cell type. I will describe differences by sex in human skeletal muscle cell type composition, cell type-level gene expression and chromatin accessibility, and bulk miRNA expression in 287 people. I will describe regulation of subcutaneous adipose gene expression by genetic variants in a meta-analysis of >2,200 people. These studies help to better understand transcription and post-transcriptional regulation of gene expression by sex and genetic regulation of gene expression.

RNA Innovation Seminar: Sundeep Kalantry, Ph.D., Professor of Human Genetics, U-M Medical School
2025-02-17 16:00
“Evolution of Mammalian Dosage Compensation”
Sundeep Kalantry, Ph.D.
Professor,
Human Genetics,
University of Michigan Medical School

In-person: Kahn Auditorium, BSRB | Hybrid link
Abstract:
The sex chromosomes pose an inequality between XX females and XY males. In therian mammals, the Y chromosome contains few unique genes, whereas the X chromosome harbors ~1000 protein-coding genes and many more noncoding loci. Excessive expression of X-linked genes in females can cause abnormal development and lethality. To equalize X-linked gene expression to that of males, females evolved X-chromosome inactivation as a dosage compensation mechanism. X-inactivation results in the silencing of most genes on one of the two Xs in females. In eutherian (‘placental’) mammals, X-inactivation requires the Xist long noncoding RNA that is expressed from and accumulates on the inactive X chromosome. Xist RNA recruits proteins that silence genes on the inactive-X. That dosage compensation requires X-inactivation and that X-inactivation requires the Xist RNA are tenets of mammalian sex chromosome biology.
Despite much work, however, whether dosage compensation requires Xist RNA and X-inactivation remains unclear. Dosage compensation is believed to have originated in therian mammals when the Y chromosome differentiated from the X chromosome. To prevent loss of genes that favored male sexual differentiation, discrete segments of the Y chromosome are thought to have undergone a series of inversions to suppress recombination with the X chromosome. Suppression of recombination is believed to have led to degeneration of genes on the Y chromosome. Due to the loss of Y-linked genes in males, females are believed to have ultimately evolved X-inactivation as a dosage compensation mechanism. Since the Y chromosome lost its gene content gradually, the need to dosage compensate X-linked genes is likely to also have arisen in a piecemeal manner. The step-wise differentiation of the X and Y chromosomes, therefore, is incompatible with chromosome-wide dosage compensation by Xist RNA and X-inactivation.
How dosage compensation can occur in the absence of Xist and X-inactivation is not known. The first Y chromosome segment to undergo differentiation from the X chromosome preceded the divergence of eutherian from metatherian mammals. Yet, Xist evolved later and only in eutherians and not in metatherians. Dosage compensation of genes in this ancestral segment of the X chromosome, therefore, is likely to have occurred prior to the advent of Xist. The ancestral form of dosage compensation is unknown but we hypothesize is still functional. We further hypothesize that this ancestral mechanism of dosage compensation was subsequently co-opted to regulate Xist when Xist arose for chromosome-wide dosage compensation through X-inactivation.
In testing the above hypotheses, we find that dosage compensation can occur in the absence of Xist and X- inactivation. We further identify an ancestral X-linked gene in the Xist- and X inactivation-independent dosage compensation mechanism. Together, our data provide insights into the origins of sex differences, mechanistically define the evolution of mammalian dosage compensation, and broadly inform how cells balance gene expression despite changes in chromosome copy number.

Bio:
Our long-standing focus is to understand mechanisms that underlie mammalian X chromosome dosage compensation, including X chromosome inactivation. X-inactivation ensures similar levels of X-linked gene expression between female and male mammals by silencing genes on one of the two X chromosomes in females. Notably, X-inactivation is also a model of sexually dimorphic epigenetic regulation, since two identical X chromosomes in female cells become transcriptionally divergent. The study of dosage compensation promises to elucidate the origins of sex differences and inform how cells balance gene expression despite changes in chromosome copy number
Links:
Kalantry Lab

RNA Collaborative Seminar Series
2025-04-09 16:00 - 17:00 | Virtual
The next RNA Collaborative Seminar will be held virtually on Wednesday, April 9th at 4 pm ET (Eastern, US/Canada), hosted by the University of Rochester Center for RNA Biology & University of Michigan Center for RNA Biomedicine. Please see below for more details and the Zoom webinar registration link, and share widely with your communities and networks.
Wednesday, April 9th at 4 pm ET
Hosted by: University of Rochester Center for RNA Biology & University of Michigan Center for RNA Biomedicine
Zoom Registration: https://us02web.zoom.us/webinar/register/WN_QYg_EA_uSkK2CB987gltVA
“Discovery and Therapeutic Applications of RNA ‘Stitching’”
Doug Anderson, PhD
Assistant Professor of Medicine, Cardiovascular Research Institute (CVRI)
Member, University of Rochester Center for RNA Biology: From Genome to Therapeutics
“High-Throughput Identification of Small Molecule Inhibitors Targeting OncoMiR-181a for Cancer Therapy”
Grace McIntyre, PhD Student
PhD Candidate, Department of Pathology, University of Michigan
“Real-time Monitoring of Ligand Recognition by a Riboswitch during Transcription”
Adrien Chauvier, PhD. Research Lab Specialist
Nils Walter Laboratory – Department of Chemistry, University of Michigan
RNA Center for Biomedicine
Moderators:
Eric J. Wagner, Ph.D.
Professor, Department of Biochemistry and Biophysics
Associate Director, Center for RNA Biology
Wilmot Cancer Institute
University of Rochester School of Medicine and Dentistry
and
Nils G. Walter, Ph.D.
Director, Center for RNA Biomedicine; Francis S. Collins Collegiate Professor of Chemistry, Biophysics, and Biological Chemistry, University of Michigan
RNA Collaborative Seminars are sponsored by the RNA Society (@RNASociety)
For more information on the RNA CSS, please visit: https://www.rnasociety.org/rna-collaborative-seminar-series
RNA Collaborative YouTube: https://www.youtube.com/channel/UC7QawzQsUqhgIqjKGTny41A

RNA Innovation Seminar: Connie Wu, Ph.D., Research Assistant Professor, Life Sciences Institute; Assistant Professor, Biomedical Engineering and Pharmaceutical Sciences, University of Michigan
2025-04-28 16:00 - 17:00 | BSRB – ABC Seminar rooms, 109 Zina Pitcher Pl, Ann Arbor, MI, 48109, United States
“Programming and probing the body: from RNA therapeutics to single-molecule detection”
Connie Wu, Ph.D.
Research Assistant Professor,
Life Sciences Institute,
Assistant Professor,
Biomedical Engineering and Pharmaceutical Sciences,
University of Michigan, U-M Medical School
In-person: ABC Seminar Rooms, BSRB | Hybrid link
Abstract:
Our lab integrates biomolecular engineering and bioanalytical chemistry approaches to develop next-generation diagnostic and therapeutic platforms. I will first discuss our work in developing multifunctional RNA systems for cancer immunotherapy applications. Leveraging RNA as a programmable scaffold, we engineer RNA nanostructures to activate multiple innate immune pathways and present additional immunomodulators. In parallel, we develop ultrasensitive single-molecule detection platforms for diagnostic applications. While ultrasensitive digital ELISA methods have unlocked a broader spectrum of disease biomarkers, achieving attomolar (10 -18 M) detection limits, the simultaneous detection of many proteins and biomolecule types with high analytical sensitivities and throughput remains a critical challenge in biomarker signature discovery. Our ongoing efforts aim to expand the ultrasensitive single-molecule detection toolkit to enable accurate high-order multiplexing and multiparametric profiling of diverse biomarker types.
Bio:
Connie Wu obtained her B.S. in chemical engineering from Yale University, where she worked with Paul Van Tassel, Ph.D., in designing porous layer-by-layer polymer films for tissue engineering applications. She pursued her Ph.D. in chemical engineering at MIT in the lab of Paula Hammond, Ph.D., where she engineered a highly potent small interfering RNA (siRNA) nanoparticle delivery system via nucleic acid engineering and polymer chemistry approaches.
Following her graduate studies, Wu transitioned to the diagnostics field for her postdoctoral research in the lab of David Walt, Ph.D., at Brigham and Women’s Hospital and the Wyss Institute at Harvard University, where she pioneered ultrasensitive single-molecule detection methods that can measure attomolar protein concentrations with versatile multiplexing capabilities. In parallel, she developed ultrasensitive digital assays for detecting the long interspersed element-1 (LINE-1) retrotransposon-encoded protein ORF1p in blood as a highly specific multi-cancer biomarker.
Wu was the recipient of multiple fellowships during her graduate and postdoctoral training, including a National Science Foundation Graduate Research Fellowship, MIT Presidential Fellowship and NIH Ruth L. Kirschstein F32 Postdoctoral Fellowship.
As part of the U-M Life Sciences Institute and the Department of Biomedical Engineering at the University of Michigan, Wu’s lab develops technologies for biomarker signature discovery and RNA therapeutic delivery, with applications across cancer and other diseases.
Links:
Connie Wu Lab – Life Sciences Institute
Biomedical Engineering
College of Pharmacy
University of Michigan Medical School

RNA Translated 2025 Feature Article
