Three-dimensional structure of a flavivirus dumbbell RNA reveals molecular details of an RNA regulator of replication

Akiyama, Benjamin M.; Graham, Monica E.; O′Donoghue, Zoe; Beckham, J. David; Kieft, Jeffrey S.

doi:10.1093/nar/gkab462

Title: Three-dimensional structure of a flavivirus dumbbell RNA reveals molecular details of an RNA regulator of replication

Journal Article · 16 June 2021 · Nucleic Acids Research

DOI: https://doi.org/10.1093/nar/gkab462 · OSTI ID:1797343

Akiyama, Benjamin M. ^[1]; Graham, Monica E. ^[2]; O′Donoghue, Zoe ^[2]; Beckham, J. David ^[3];

^[4]

Department of Biochemistry and Molecular Genetics, Aurora, CO 80045, USA
Department of Immunology and Microbiology, Aurora, CO 80045, USA
Department of Immunology and Microbiology, Aurora, CO 80045, USA, Department of Medicine Division of Infectious Diseases, Aurora, CO 80045, USA
Department of Biochemistry and Molecular Genetics, Aurora, CO 80045, USA, RNA BioScience Initiative, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA

Abstract Mosquito-borne flaviviruses (MBFVs) including dengue, West Nile, yellow fever, and Zika viruses have an RNA genome encoding one open reading frame flanked by 5′ and 3′ untranslated regions (UTRs). The 3′ UTRs of MBFVs contain regions of high sequence conservation in structured RNA elements known as dumbbells (DBs). DBs regulate translation and replication of the viral RNA genome, functions proposed to depend on the formation of an RNA pseudoknot. To understand how DB structure provides this function, we solved the x-ray crystal structure of the Donggang virus DB to 2.1Å resolution and used structural modeling to reveal the details of its three-dimensional fold. The structure confirmed the predicted pseudoknot and molecular modeling revealed how conserved sequences form a four-way junction that appears to stabilize the pseudoknot. Single-molecule FRET suggests that the DB pseudoknot is a stable element that can regulate the switch between translation and replication during the viral lifecycle by modulating long-range RNA conformational changes.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1797343

Journal Information:: Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 12 Vol. 49; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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