Detecting Structural interactions within the Coxsackievirus B3 Genomic RNA Using Modern Computational Approaches

Presenter Information

Chris HornFollow

Advisor Information

William Tapprich

Location

249

Presentation Type

Oral Presentation

Start Date

1-3-2019 9:00 AM

End Date

1-3-2019 10:15 AM

Abstract

The 5’ untranslated region (5’UTR) of enteroviruses contain a highly structured and complex element known as an internal ribosome entry site (IRES). The IRES itself constitutes multiple discrete domains that are interconnected via less structured regions of RNA. Ample evidence has shown that the proper folding and functioning of the IRES is essential to the efficiency of viral genome replication and translation as well as viral virulence. We characterized the structure of the Coxsackievirus B3 (CVB3) strain 28 5’UTR, a cardiovirulent member of the enteroviridae family, using small molecule probes in solution. The reactivity profile of strain 28 was then input into a computational algorithm designed to predict RNA secondary structure via a combination of sequence homology and experimentally generated probing data. Our results indicate a restructuring of major domains, newly identified long-range interactions, and intrinsically unstructured regions of RNA. Taken together, these results contribute to a model for enteroviral 5’UTR IRES elements that link structure to function.

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Mar 1st, 9:00 AM Mar 1st, 10:15 AM

Detecting Structural interactions within the Coxsackievirus B3 Genomic RNA Using Modern Computational Approaches

249

The 5’ untranslated region (5’UTR) of enteroviruses contain a highly structured and complex element known as an internal ribosome entry site (IRES). The IRES itself constitutes multiple discrete domains that are interconnected via less structured regions of RNA. Ample evidence has shown that the proper folding and functioning of the IRES is essential to the efficiency of viral genome replication and translation as well as viral virulence. We characterized the structure of the Coxsackievirus B3 (CVB3) strain 28 5’UTR, a cardiovirulent member of the enteroviridae family, using small molecule probes in solution. The reactivity profile of strain 28 was then input into a computational algorithm designed to predict RNA secondary structure via a combination of sequence homology and experimentally generated probing data. Our results indicate a restructuring of major domains, newly identified long-range interactions, and intrinsically unstructured regions of RNA. Taken together, these results contribute to a model for enteroviral 5’UTR IRES elements that link structure to function.