The RNA Transcript, January 18, 2021 |
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Repurposing Prostate Cancer Drug for COVID-19
In our September 2020 issue of RNA Translated, 2020 the year of the RNA virus, we presented how University of Michigan (U-M) Center for RNA Biomedicine's scientists pivoted their research to address the COVID-19 pandemic. One of them is Dr. Chinnaiyan and his team of prostate cancer researchers
who focused on two proteins that are involved in giving access to the virus into a host cell. The production of these two proteins is regulated by male hormones. With J. Sexton from the U-M Center for Drug Repurposing, the collaborators looked at repurposing well-known drugs used in prostate cancer to block a receptor for male hormone, and prevent the coronavirus from entering a host cell.
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“We hope that these findings may partly explain why males have higher hospitalization and mortality rates than females, and also suggest that transcriptional inhibition of key host factors may have potential in preventing or treating COVID-19. A number of clinical trials in COVID-19 patients have been initiated with drugs that were previously used to treat prostate cancer,” says Dr. Chinnaiyan.
The results from the current study are published in the January 5, 2021, Proceedings of the National Academy of Sciences.
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Targeting transcriptional regulation of SARS-CoV-2 entry factors ACE2 and TMPRSS2
Yuanyuan Qiao, Xiao-Ming Wang, Rahul Mannan, Sethuramasundaram Pitchiaya, Yuping Zhang, Jesse W. Wotring, Lanbo Xiao, Dan R. Robinson, Yi-Mi Wu, Jean Ching-Yi Tien, Xuhong Cao, Stephanie A. Simko, Ingrid J. Apel, Pushpinder Bawa, Steven Kregel, Sathiya P. Narayanan, Gregory Raskind, Stephanie J. Ellison, Abhijit Parolia, Sylvia Zelenka-Wang, Lisa McMurry, Fengyun Su, Rui Wang, Yunhui Cheng, Andrew D. Delekta, Zejie Mei, Carla D. Pretto, Shaomeng Wang, Rohit Mehra, Jonathan Z. Sexton, and Arul M. Chinnaiyan, PNAS January 5, 2021 118 (1) e2021450118; first published December 11, 2020; https://doi.org/10.1073/pnas.2021450118
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Graduate Student, Environmental Health Sciences
School of Public Health
"My research is focused on uncovering the biological basis for racial disparities in breast cancer by exploring the relationship between normal mammary stem cells, genetics, and environmental exposures. I believe that this is a pressing public health and environmental justice issue because striking racial disparities in breast cancer have been known for decades, yet today there is still little known about their biological basis."
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Monday, January 18, 3:00 pm | U-M Health Sciences 2021 MLK Keynote
"Where Do We Go From Here: Body Politics and Movement Towards Racial Empowerment"
Monique Butler, M.D., U-M Kinesiology alumna and Chief Medical Officer for HCA Healthcare North Florida Division
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Monday, January 18, 3:00 pm | U-M Human Genetics, Medical School
ZOOM MEETING ID: 947 7324 2869
"Molecular and Functional Characterization of Conserved and Divergent Features of Mammalian Spermatogenesis"
Adrienne Shami, Advisor: S Hammoud
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Tuesday, January 19, 3:00–4:00 pm | Harvard Medical School Initiative for RNA Medicine Seminar
"Revealing Hidden Biology with Spatial, High-Plex Transcriptional Profiling on the NanoString GeoMx Platform"
Sarah Warren, Ph.D., Senior Director, Translational Science, R&D, NanoString Technologies
"Enabling spatial mapping and quantification of RNA in situ with RNAscope, miRNAscope, and BaseScope"
Emily Martersteck, Field Application Scientist, Bio-Techne
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Tuesday, January 19, 5:00 pm | Harvard Medical School Initiative for RNA Medicine Seminar
“Processing, conformation and function of circular and long ncRNAs”
Ling-Ling Chen, Ph.D., M.B.A., Principal Investigator, Shanghai Institute of Biochemistry and Cell Biology, (Center for Excellence in Molecular Cell Science), Chinese Academy of Sciences
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Monday, January 25, 9:00–10:00 am EST (please note the time change) | U-M Center for RNA Biomedicine, RNA Innovation Seminar Series
"The RNA exosome complex: the Dr Jekyll and Mr Hyde of RNA degradation"
Keywords: molecular mechanisms, RNA, ribosome, biochemistry, cryo-EM, X-ray crystallography
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Wednesday, January 27, 4:00 pm EST | U-M Computational medicine and bioinformatics Seminar – sponsored by DCMB
"Cumulus: cloud-based data analysis framework for large-scale single-cell and single-nucleus genomics"
Dr. Bo Li, Ph.D., is an assistant professor of medicine at Harvard Medical School, the director of Bioinformatics and Computational Biology at Center for Immunology Inflammatory Diseases, Massachusetts General Hospital, and an associate member of the Broad Institute of MIT and Harvard.
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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 is a recent highlight.
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Transcriptomic signatures and repurposing drugs for COVID-19 patients: findings of bioinformatics analyses, GuobingLi, ShashaRuan, XiaoluZhao, QiLiu, Yali Dou, Fengbiao Mao, Computational and Structural Biotechnology Journal, Volume 19, 2021, Pages 1-15,
Abstract
... we systematically evaluated the effect of SARS-CoV-2 on gene expression of both lung tissue and blood from COVID-19 patients using transcriptome profiling....
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Amilorides inhibit SARS-CoV-2 replication in vitro by targeting RNA structures, Martina Zafferani, Christina Haddad, Le Luo, Jesse Davila-Calderon, Liang Yuan-Chiu, Christian Shema Mugisha, Adeline G. Monaghan, Andrew A. Kennedy, Joseph D. Yesselman, Robert R. Gifford, Andrew W. Tai, Sebla B. Kutluay, Mei-Ling Li,
Gary Brewer, Blanton S. Tolbert, Amanda E. Hargrove, bioRxiv, 06 December 2020, https://doi.org/10.1101/2020.12.05.409821
Summary and Outlook
In summary, we herein identified drug-like small molecules that reduce SARS-CoV-2 replication and are the first antivirals to target the conserved RNA stem loops in the 5’- end region of SARS-CoV-2. Work is underway to further characterize the mode of action of these ligands, particularly putative impacts on RNA:protein interactions and specific steps in the viral replication cycle. Once characterized, we expect these amiloride-based ligands to serve as chemical biology tools to help understand CoV RNA molecular biology, such as N-dependent genome packaging and other cellular stages of the viral RNA replication process. Importantly, we have established an efficient framework to identify novel RNA-targeted CoV antivirals that will serve not only the SARS-CoV-2 pandemic but future coronavirus pandemics.
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Disease-associated mutations in mitochondrial precursor tRNAs affect binding, m1R9 methylation and tRNA processing by mtRNase P
2020 Dec 30; rna.077198.120. doi: 10.1261/rna.077198.120.
Abstract
Mitochondrial diseases linked to mutations in mitochondrial (mt) tRNA sequences are common. However, the contributions of these tRNA mutations to the development of diseases is mostly unknown. Mutations may affect interactions with (mt)tRNA maturation enzymes or protein synthesis machinery leading to mitochondrial dysfunction...
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