PT  - JOURNAL ARTICLE
AU  - Benjamin M. Akiyama
AU  - Monica E. Graham
AU  - Zoe O′Donoghue
AU  - J. David Beckham
AU  - Jeffrey S. Kieft
TI  - Three-dimensional structure of a flavivirus dumbbell RNA reveals molecular details of an RNA regulator of replication
AID  - 10.1101/2020.09.17.300806
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.17.300806
4099  - http://biorxiv.org/content/early/2020/09/17/2020.09.17.300806.short
4100  - http://biorxiv.org/content/early/2020/09/17/2020.09.17.300806.full
AB  - 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) that 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 used x-ray crystallography and 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.Competing Interest StatementThe authors have declared no competing interest.