Special COVID-19 Symposium

Thursday, December 10, 2020, 1:15 pm to 2:15 pm EST

Chair: Ruth Lehmann, Whitehead Institute for Biomedical Research

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Montserrat Bárcena

Leiden University Medical Center, The Netherland
The Coronavirus Escape Room

 

Rouskin

Silvi Rouskin

Whitehead Institute
Structure of the Full SARS-CoV-2 RNA Genome in Infected Cells

Our Special COVID-19 Symposium contains talks from two of the top COVID-19 researchers. Each speaker will provide an overview of their current research followed by a 5-minute Q&A moderated by Dr. Lehmann.

The Coronavirus Escape Room 
Montserrat Bárcena
Coronavirus replicate their genomes in characteristic double-membrane vesicles (DMVs) that appeared to be sealed,  making it unclear how the newly made viral RNA could be exported to the cytosol for translation and packaging.  We unveiled a crown-shaped molecular pore that connects the DMV lumen with the cytosol and established that a hexameric assembly of a large coronavirus transmembrane protein forms its core. This molecular pore likely constitutes the long-sought pathway for RNA export and defines a new coronavirus-specific drug target.

Structure of the Full SARS-CoV-2 RNA Genome in Infected Cells
Silvi Rouskin
Silvi's lab analyzed the secondary structure of the entire SARS-CoV-2 genome in infected cells at single nucleotide resolution using dimethyl sulfate mutational profiling with sequencing(DMS-MaPseq). Their results reveal previously undescribed structures within criticalregulatory elements such as the genomic transcription-regulating sequences (TRSs).Contrary to previous studies, their in-cell data show that the structure of the frameshiftelement, which is a major drug target, is drastically different from prevailing in vitro models.  Based on their discoveries, they proposed a unique mechanism of ribosomal frameshifting on the viral RNA, suggesting that frameshifting is controlled by the formation of alternative RNA structures that either block the ribosome to induce frameshifting or allow the ribosome to continue translation.