The RNA Transcript, July 19, 2021 |
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For most organisms, DNA sequences are available, but the complete RNA sequences are not. Here, we call for technologies to sequence full-length RNAs with all their modifications.
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Sydney Rosenblum, a graduate student in Rackham Graduate School,
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Sometimes it takes exploration outside our usual interests to find our true passion. This is what happened to Sydney Rosenblum, now a graduate student in Rackham Graduate School Program in Chemical Biology, in Professor Amanda Garner’s lab. In high school, Sydney felt that “science was not for her,” somewhat irrelevant or too abstract, until she serendipitously took a biotechnology class offered through a special program sponsored by the State of California. Obscure science became hands-on, and she was hooked. “It was really cool to actually be able to manipulate biology in the lab,” she fondly recalls. “It was also very exciting to learn about new pivotal discoveries, like DNA sequencing, things that you usually learn about only until much later.”
Photo: Sydney Rosenblum cultures mammalian cells in a laminar flow hood. Credit: Sara Khan
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Friday, July 23, 12:00 pm ET | Genetic Engineering and Biotechnology News, The Women in Science Webinar Series
"Development of the mRNA Therapeutic—Not Warp Speed!" with Dr. Katalin Karikó who will talk about her pioneering research in mRNA vaccine technology. The Hungarian-born biochemist’s discoveries provided scientists with the tools necessary to develop mRNA vaccines for COVID-19.
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August 6–7, 3rd International Webinar on Nucleic Acids & CRISPR
"Cracking the code of DNA and RNA: New insights into the structure and functions of nucleic acids"
This event is a broad audience gathering for exploring the advancement in DNA, RNA, epigenetics, and innovative techniques at molecular and chemical levels.
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September 9–10, Rust Belt RNA Meeting 2021, Columbus, Ohio
Keynote speaker: Professor Hashim Al-Hashimi, Duke University School of Medicine
We are pleased to be a sponsor of this event.
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For press releases and blog articles about your upcoming top journal publications,
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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 are recent highlights.
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Cotranscriptional splicing efficiencies differ within genes and between cell types,Karan Bedi, Brian Magnuson, Ishwarya Venkata Narayanan, Michelle T. Paulsen, Thomas E. Wilson, and Mats Ljungman, RNA July 2021 27: 829-840; doi:10.1261/rna.078662.120
In this article published in the journal RNA, Karan Bedi, a bioinformatician in Mats Ljungman’s lab, Department of Radiation Oncology at the University of Michigan Medical School, investigated the efficiency of splicing across different human cell types. The results were surprising in that the splicing process appears to be quite inefficient, leaving most intronic sequences untouched as the transcripts are being synthesized. The study also reports variable patterns between the different introns within a gene and across cell lines, and it further highlights the complexity of how newly transcripts are processed into mature mRNAs.
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The RNA helicase DHX36/G4R1 modulates C9orf72 GGGGCC hexanucleotide repeat- associated translation, Yi-Ju Tseng, Siara N. Sandwith, Katelyn M. Green, Antonio E. Chambers, Amy Krans, Heather M. Raimer, Meredith E. Sharlow, Michael A. Reisinger, Adam E. Richardson, Eric D. Routh, Melissa A. Smaldino, Yuh-Hwa Wang, James P. Vaughn, Peter K. Todd, Philip J. Smaldino, Journal of Biological Chemistry, 2021 Jun 23;100914. doi: 10.1016/j.jbc.2021.100914
Keywords: C9ORF72; DHX36/G4R1/RHAU; DNA helicase; Dipeptide repeat proteins (DPRs); Fragile X; G-quadruplex; Huntington disease; RNA helicase; Repeat-associated non-AUG translation (RAN); amyotrophic lateral sclerosis (ALS) (Lou Gehrig disease).
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Previously considered “difficult to drug” on a structural and selectivity basis, considerable efforts in academia and industry are now being focused on targeting RNA as a therapeutic modality. These efforts are driven based on both the biological significance of RNAs, as well as a growing number of studies implicating aberrant RNA biology in many human diseases.
While biologic approaches continue to play an impactful and ever-growing role in RNA-targeted drug discovery, considerable efforts are now being devoted toward the targeting of RNAs with small molecules. In the issue, both a diversity of RNA types, as well as strategies for small molecule discovery, are highlighted.
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Small-molecule inhibitors targeting Polycomb repressive complex 1 RING domain. Shukla, S., Ying, W., Gray, F. et al. Nat Chem Biol 17, 784–793 (2021). https://doi.org/10.1038/s41589-021-00815-5
Abstract: Polycomb repressive complex 1 (PRC1) is an essential chromatin-modifying complex that monoubiquitinates histone H2A and is involved in maintaining the repressed chromatin state. Emerging evidence suggests PRC1 activity in various cancers, rationalizing the need for small-molecule inhibitors with well-defined mechanisms of action. Here, we describe the development of compounds that directly bind to RING1B–BMI1, the heterodimeric complex constituting the E3 ligase activity of PRC1. These compounds block the association of RING1B–BMI1 with chromatin and inhibit H2A ubiquitination. Structural studies demonstrate that these inhibitors bind to RING1B by inducing the formation of a hydrophobic pocket in the RING domain. Our PRC1 inhibitor, RB-3, decreases the global level of H2A ubiquitination and induces differentiation in leukemia cell lines and primary acute myeloid leukemia (AML) samples. In summary, we demonstrate that targeting the PRC1 RING domain with small molecules is feasible, and RB-3 represents a valuable chemical tool to study PRC1 biology.
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