Webinar: Targeting RNA Structure as a Therapeutic Strategy

January 19th, 2022 14:00 EST | January 19th, 2022 20:00 CET

Across all domains of life and in viruses, RNA structures play critical roles in regulating gene expression. Although it had been known for decades that many RNAs such as riboswitches adopt multiple structures, traditional methods of characterizing RNA structures could either only determine the average structure (e.g., DMS-seq, SHAPE) or only be applied outside of cells (e.g., XRD, NMR). In order to characterize ensembles of alternative RNA structures inside living cells, Dr. Rouskin’s lab recently developed the DREEM algorithm, which deconvolutes single-molecule chemical probing data (DMS-MaPseq) to identify alternative structures.

Dr. Rouskin's lab characterized the ensembles of secondary structures across the entire RNA genome of SARS-CoV-2 during infection of VeroE6 and Huh7 cells. They found that at least half of the genome forms alternative structures in cells. Of particular interest, was the frameshifting stimulation element (FSE), which causes a fraction of ribosomes to slip backward by 1 nt, bypass a stop codon in the middle of open reading frame 1 and translate five essential proteins, including the viral RNA polymerase. Numerous studies have shown that inhibiting ribosomal frameshifting impairs the replication of coronaviruses, including SARS-CoV-2. Surprisingly, they found that sequences flanking the FSE upregulate ribosomal frameshifting, and furthermore that one of the alternative structures of the FSE involves an RNA-RNA interaction with an element 1.2 kb downstream.

Section Highlights

• Determine RNA Structure in Cells
• Quantify Alternative Conformations
• Target RNA Structure

Webinar Recording

Webinar Speaker

Dr. Rouskin specializes in research on the RNA structure and how its functions impact viral infections and human disease in order to design novel therapeutic approaches. She immigrated from Bulgaria to the United States alone as a teenager to pursue a career in science. At sixteen, she became a freshman at Florida Institute of Technology and obtained a BS in physics. Silvia did her Ph.D. in Jonathan Weissman’s lab at UCSF and, in lieu of a traditional postdoctoral fellowship, started her own research center at the Whitehead Institute for Biomedical Research at MIT. Currently, Silvia is an assistant professor at Harvard Medical School in the department of Microbiology.