The RNA Transcript, June 21, 2021

Today is the longest (or shortest)
day of the year. Happy solstice!
As we end the 2020–21 academic year, we’re still pondering the impact of RNA research on the pandemic that is changing the world we live in. As RNA scientists, we applaud the mRNA vaccine development and how scientists pivoted their research to contribute to SARS-CoV-2 and COVID-19 research. These extraordinary scientific achievements and the pandemic are also revealing deep social justice issues, and we are thrilled by the recent announcement that a billion doses of COVID-19 mRNA vaccines will be made available to the world for free. Together, the RNA scientific community is saving millions of lives.

Closer to home, this year has also been an unexpected opportunity to further strengthen our local, national, and international outreach. We offered 17 one-hour Zoom webinars, our RNA Innovation Seminar Series, where RNA scientists presented their latest work on a broad range of topics, from foundational biology to potential therapeutics. These seminars fostered new insights and synergies for potential collaborations. Our members were given the opportunity to meet individually with these presenters and explore possible partnerships.

Welcome to Jun Hee Lee, new member of the Center for RNA Biomedicine!

Dr. Lee's lab studies the relationship between stress, aging and metabolism, focusing on the following projects: (1) Stress-inducible Sestrins and their role in age- and obesity-associated metabolic pathologies, (2) Biochemical mechanisms underlying physiological functions of Sestrins, (3) Pathogenetic mechanisms of how autophagy is abrogated in human diseases including non-alcoholic fatty liver disease (NAFLD) and movement disorders, (4) Stress-induced protein inclusions and RNA granules, (5) Single cell-level understanding of stress-induced transcriptome changes, and (6) Technology development for single-cell and subcellular studies of spatial transcriptome and proteome.

Tuesday, June 22, 1:00–4:30 pm ET | U-M Single Cell Spatial Analysis Program

"Single Cell Spatial Analysis Program Kick Off Symposium"
Featuring Keynote Speaker Dr. Tzumin Lee, Group Leader, Janelia Research Campus, HHMI
Tuesday–Thusday, June 23–25 | UMass Medical School, RNA Therapeutics Institute

2021 RNA Therapeutics Institute Symposium: "From Concept to Clinic"
Thursday, June 24, 10:00 am EST | University of Michigan, Bioinformatics Dissertation Defense

"Disentangling the 4D Nucleome"
Stephen Lindsly; advisor: Indika Rajapakse
Thursday, June 24, 11:00 am EST | University of Michigan, Bioinformatics Dissertation Defense

"Advancement of Molecular Mechanics based Drug Discovery through the Use of Machine Learning"
Murchtricia Jones; advisor: Charles Brooks
Thursday, June 25, 10:00 am EST | University of Michigan, Neuroscience Dissertation Defense

"More than Clearing the Clutter: The Imperative Role of Efferocytosis in Repair and Immune Reprogramming in the Damaged Nervous System"
Lucas Huffman; advisor: Roman Giger
Tuesday, June 29, 2021, 3:00 pm ET | HMS Harvard Medical School Initiative for RNA Medicine Seminar 
ZOOM, Password: 770277, Meeting ID: 963 4075 0975
“Running with beacons; illuminating the path of red blood cell-derived extracellular vesicles”
Ionita Ghiran, M.D., Associate Professor of Medicine, Beth Israel Deaconess Medical Center
Wednesday, June 30, 4:00 pm ET | RNA Collaborative Seminar Series, hosted by the University of Michigan Center for RNA Biomedicine
Join the discussion on Discord.

“Revealing New Functions for Ancient RNA Modifying Enzymes in Health and Disease”
“Dynamic multivalent interactions drive mammalian RNA regulation”

"Characterizing cellular RNA-protein interaction networks with chemical probes"

Moderator: Nils G. Walter
For press releases and blog articles about your upcoming top journal publications,

Our members' publications are available through Altmetric. Five queries are currently available: "RNA," "microRNA," "Transcriptome," "Translation," and "Molecule." Please make sure to have at least one of these key words in your title or abstract. Below are recent highlights.
Sleep loss drives brain region- and cell type-specific alterations in ribosome-associated transcripts involved in synaptic plasticity and cellular timekeeping
Carlos Puentes-Mestril, James Delorme, Lijing Wang, Marcus Donnelly, Donald Popke, Sha Jiang and Sara J. Aton, Journal of Neuroscience, 17 May 2021, JN-RM-1883-20; DOI:

Significance Statement: Sleep loss-driven changes in transcript and protein abundance have been used as a means to better understand the function of sleep for the brain. Here we use translating ribosome affinity purification (TRAP) to characterize changes in abundance of ribosome-associated transcripts in excitatory and inhibitory neurons in mouse hippocampus and neocortex after a brief period of sleep or sleep loss. We show that these changes are not uniform, but are generally more pronounced in excitatory neurons than inhibitory neurons, and more pronounced in neocortex than in hippocampus.
ELOF1 is a transcription-coupled DNA repair factor that promotes DNA damage-induced RNAPII ubiquitylation, Yana van der Weegen, Klaas de Lint, Diana van den Heuvel, Yuka Nakazawa, Ishwarya V. Narayanan, Noud Klaassen, Annelotte P. Wondergem, Marta San Martin Alonso, Shivani Rampersad, Yuichiro Hara, Kana Kato, Mayuko Shimada, Sylvie M. Noordermeer, Mats Ljungman, Tomoo Ogi, Rob M.F. Wolthuis, and Martijn S. Luijsterburg, Nature Cell Biology, 23:595-607, 2021,

Summary: Cells employ transcription-coupled repair (TCR) to eliminate transcription-blocking DNA lesions. The binding of the TCR-specific repair factor CSB triggers DNA damage-induced ubiquitylation of RNA polymerase II (RNAPII) at a single lysine (K1268) by the CRL4CSA ubiquitin ligase. However, how the CRL4CSA ligase is specifically directed toward the K1268 site is unknown. Here, we identify ELOF1 as the missing link that facilitates RNAPII ubiquitylation, a key signal for the assembly of downstream repair factors. This function requires its constitutive interaction with RNAPII close to the K1268 site, revealing ELOF1 as a specificity factor that positions CRL4CSA for optimal RNAPII ubiquitylation. Furthermore, drug-genetic interaction screening reveals an unanticipated compensatory TCR pathway in which ELOF1 together with known factors DOT1L and HIRA protect CSB-deficient cells from collisions between transcription and replication machineries. Our study provides a genetic framework of the transcription stress response and reveals key insights into the molecular mechanism of TCR.
A CSB-PAF1C axis restores processive transcription elongation after DNA damage repair, Diana van den Heuvel, Cornelia G. Spruijt, Román González-Prieto, Angela Kragten, Michelle T. Paulsen, Di Zhou, Haoyu Wu, Katja Apelt, Yana van der Weegen, Kevin Yang, Madelon Dijk, Lucia Daxinger, Jurgen A. Marteijn, Alfred C.O. Vertegaal, Mats Ljungman, Michiel Vermeulen, and Martijn S. Luijsterburg, Nature Communications, 12:1342, 2021. PMC7910549

Abstract: Bulky DNA lesions in transcribed strands block RNA polymerase II (RNAPII) elongation and induce a genome-wide transcriptional arrest. The transcription-coupled repair (TCR) pathway efficiently removes transcription-blocking DNA lesions, but how transcription is restored in the genome following DNA repair remains unresolved. Here, we find that the TCR-specific CSB protein loads the PAF1 complex (PAF1C) onto RNAPII in promoter-proximal regions in response to DNA damage. .... Our findings expose the molecular basis for a non-canonical PAF1C-dependent pathway that restores transcription throughout the human genome after genotoxic stress.

Subject terms: Nucleotide excision repair, Protein-protein interaction networks, Transcription
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