The RNA Transcript, January 31, 2022 |
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RNA Faculty Candidate Seminar |
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Koutmou and Koutmos results published in PNAS |
A U-M team of biochemists is reframing the understanding of the biology of a class of enzymes called Pseudouridine Synthases (Pus enzymes). |
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This novel understanding of pseudouridine biology could have important therapeutic implications because the dysregulation of Pus enzymes is linked to inherited diseases impacting muscle and brain function, such as progressive mitochondrial myopathy and sideroblastic anemia (MLASA). Furthermore, these enzymes also catalyze pseudouridine incorporation into RNA viral genomes, including that of SARS-CoV-2. As such, Pus enzymes present a potential new target for the development of therapeutics. Read more >>
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Four U-M RNA Center Members named AAAS fellows
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Charles Burant, Dr. Robert C. and Veronica Atkins Professor of Metabolism, professor of internal medicine, and of molecular and integrative physiology and director of the A. Alfred Taubman Medical Research Institute, Medical School; and professor of nutritional sciences, School of Public Health, for distinctive molecular and metabolomic research on insulin resistance, therapy for diabetes and management of obesity combined with stimulation of physical activity. |
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Mats Ljungman, Co-Director, Center for RNA Biomedicine, professor of radiation oncology, Medical School; and professor of environmental health sciences, School of Public Health, for distinguished contributions to the field of computational medicine and bioinformation through scientific and leadership achievements through contributions and dedication to the RNA community of research. |
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Melanie Ohi, Rowena G. Matthews Collegiate Professor in the Life Sciences, Life Sciences Institute; professor of cell and developmental biology, Medical School, for distinguished contributions to the field of structural biology, particularly structure/function discoveries about secretion systems of pathogenic bacteria, and for expanding access to cryo-electron microscopy through education. |
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Trisha Wittkopp, Sally L. Allen Collegiate Professor of Ecology and Evolutionary Biology and Molecular, Cellular and Developmental Biology, Arthur F. Thurnau Professor, and professor of ecology and evolutionary biology, and of molecular, cellular and developmental biology, LSA, for outstanding contributions to the field of evolutionary genetics, including uncovering genetic and genomic changes responsible for phenotypic differences within and between species, and for exceptional teaching and mentoring. |
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Congratulations to all U-M Awardees
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Introducing:
The RNA Lightning Talk Workshop and Competition
sponsored by the RNA Collaborative and the RNA Society
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Are you passionate about your research? Want to share your love of science with the world? Need help with presentation skills? Join the RNA Collaborative Lightning Talks workshop!
You will learn how to use storytelling to present your ideas and connect with your audience. Never given a presentation before? Join us in learning best practices! Given plenty of talks? Join us for new techniques and to sharpen your skills!
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Following the workshop, participants will be ready to make a 5 minute lightning talk. Videos will be judged and the winners will receive prize money and membership to the RNA Society. All participants will receive a certificate of recognition. |
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Awards:
- 1st place $150
- 2nd place $100
- 3rd place $75
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Important dates:
- March 1st - Applications Due
- April 1st - Invitations sent
- April 27th - Workshop
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U-M Advanced Genomics Core Upgrades Single Cell Offerings with New 10x Genomics Chromium X |
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The BRCF Advanced Genomics Core is pleased to announce the addition of the 10x Genomics Chromium X, a next-generation microfluidic platform, to our stable of single-cell instrumentation. The Chromium X acquisition ushers in the ability to execute High Throughput (HT) gene expression or immune profiling experiments within the AGC. The instrument chip now allows for up to 16 samples to be loaded per run, doubling the core’s sample processing capacity. Along with allowing more projects to enter the facility simultaneously, the Chromium X provides investigators more flexibility when planning experiments. Using HT reagents, you can target up to 20,000 cells/nuclei per individual reaction or up to 60,000 cells/nuclei when using multiplex reagents (Hashtag or Cellplex). Both the Gene Expression and Immune Profiling reagents are stocked and available for immediate request. Pricing for HT experiments can be generated using our AGC Cost Estimator.
We anticipate that high throughput single-cell analysis will unlock a new level of biological insight and are excited to expand our offerings. As always, we are happy to help you plan your single-cell experiments to make the best use of our state-of-the-art instrumentation. Please contact advanced-genomics@umich.edu with any questions. |
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U-M RNA Oral Dissertation Defense |
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"Investigating the Proliferation-Quiescence Decision in Tissues and in Cancer Cells"
Monday, January 31, 2022
12:00 pm - 1:00 pm
BSB 4222
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----Wednesday, February 9, 2022
----10:00 am - 11:00 am
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"CircRNA subclasses and functions"
"The role of long noncoding RNAs in brain aging"
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U-M Center for RNA Biomedicine, Faculty Candidate Seminar |
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"Mechanisms of co-transcriptional ribonucleoprotein assembly"
Johns Hopkins University
Monday, February 14, 2022
4:00 pm - 5:00 pm
BSRB, ABC Seminar rooms (hybrid)
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Co-hosted by the Department of Biological Chemistry and the Program in Biophysics |
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Excited about joining a well-funded, dynamic, collaborative & creative team and leveraging our $1.5 billion annual R&D expenditure University of Michigan with vibrant RNA community? Interested to learn RNA biology & single molecule microscopy in beautiful Ann Arbor? Send cover & application with three references to nwalter@umich.edu. |
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Our members' publications are available through Altmetrics. Queries are currently available: CRISPR, microRNA, molecule, RNA, RNA therapeutics, transcriptome, and translation. Below are recent highlights.
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Pseudouridine synthase 7 is an opportunistic enzyme that binds and modifies substrates with diverse sequences and structures, Meredith K. Purchal, Daniel E. Eyler, Mehmet Tardu, Monika K. Franco, Megan M. Korn, Taslima Khan, Ryan McNassor, Rachel Giles, Katherine Lev, Hari Sharma, Jeremy Monroe, Leena Mallik, Markos Koutmos and Kristin S. Koutmou, Proceedings of the National Academy of Sciences, 1/25/2022, DOI: 10.1073/pnas.2109708119
Pseudouridine is among the most-abundant RNA modifications. We present a framework for conceptualizing how eukaryotic pseudouridine synthases select their substrates. This work reveals the structure of yeast pseudouridine synthase 7 (Pus7) and presents cell-based and biochemical investigations of enzyme binding and activity. We demonstrate that Pus7 interacts promiscuously with RNAs containing UGUAR sequences. Our observations raise the question of why these enzymes only modify <5% of UGUAR sequences in the transcriptome, suggesting that factors beyond inherent enzyme properties—such as protein localization, local RNA structure, and RNA–protein interactions—principally shape Pus7 substrate selection. These findings support a role for Pus7 in providing cells with a mechanism to rapidly alter protein synthesis in response to cellular conditions.
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Cas11 enables genome engineering in human cells with compact CRISPR-Cas3 systems Renke Tan, Ryan K. Krueger, Max J. Gramelspacher, Xufei Zhou, Yibei Xiao, Ailong Ke, Zhonggang Hou, Yan Zhang , Molecular Cell (2021), DOI: 10.1016/j.molcel.2021.12.032
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 CRISPRs, are under-exploited for eukaryotic applications. Here, we report the adoption of a minimal CRISPR-Cas3 from Neisseria lactamica (Nla) type I-C system to create targeted large deletions in the human genome. RNP delivery of its processive Cas3 nuclease and target recognition complex Cascade can confer ∼95% editing efficiency. Unexpectedly, NlaCascade assembly in bacteria requires internal translation of a hidden component Cas11 from within the cas8 gene. Furthermore, expressing a separately encoded NlaCas11 is the key to enable plasmid- and mRNA-based editing in human cells. Finally, we demonstrate that supplying cas11 is a universal strategy to systematically implement divergent I-C, I-D, and I-B CRISPR-Cas3 editors with compact sizes, distinct PAM preferences, and guide orthogonality. These findings greatly expand our ability to engineer long-range genome edits.
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