Poster abstracts

Poster number 66 submitted by Jacob Horn

Comprehensive analysis of SARS-CoV-2 5’ UTR functional elements that facilitate evasion of Nsp1-mediated translational shutdown

Jacob S. Horn (Cellular and Molecular Biology Program, University of Michigan), Rachel Niederer (Department of Biological Chemistry, University of Michigan)

Abstract:
SARS-CoV-2 protein Nsp1 induces a global translation shutdown in host cells upon infection. The viral genome can escape the translational shutdown via secondary structure in its 5’ untranslated region (UTR). The first hairpin structure, stem-loop 1 (SL1), has been identified as necessary and sufficient to evade Nsp1-mediated translation shutdown. Despite proven functional roles within the 5’ UTR, other elements remain understudied. We wondered if the 5’ UTR has other functional regions that might influence translational control and evasion of the translational shutdown. We will use a recently developed method called direct analysis of ribosome targeting (DART), a high throughput method that tests the ribosome recruitment ability of thousands of 5’ UTRs. We will generate a diverse pool of sequences that will allow thorough examination of each region of the 5’ UTR and its role in evasion. The pool will include all known natural, scanning, structural, and compensatory mutations. Completing DART with and without Nsp1 will elucidate what elements facilitate the evasion of Nsp1-mediated translational shutdown.

Keywords: 5 UTR, Translation, SARS-CoV-2