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The 3\u2032 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 2.1\u00c5 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.<\/jats:p>","DOI":"10.1093\/nar\/gkab462","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T15:17:58Z","timestamp":1621264678000},"page":"7122-7138","source":"Crossref","is-referenced-by-count":36,"title":["Three-dimensional structure of a flavivirus dumbbell RNA reveals molecular details of an RNA regulator of replication"],"prefix":"10.1093","volume":"49","author":[{"given":"Benjamin M","family":"Akiyama","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica E","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"O\u2032Donoghue","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00a0David","family":"Beckham","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, Aurora, CO 80045, USA"},{"name":"Department of Medicine Division of Infectious Diseases, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3718-1891","authenticated-orcid":false,"given":"Jeffrey\u00a0S","family":"Kieft","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, Aurora, CO 80045, USA"},{"name":"RNA BioScience Initiative, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,6,16]]},"reference":[{"key":"2021070901240223400_B1","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"2021070901240223400_B2","doi-asserted-by":"crossref","first-page":"S98","DOI":"10.1038\/nm1144","article-title":"Emerging flaviviruses: the spread and resurgence of Japanese encephalitis, West Nile and dengue viruses","volume":"10","author":"Mackenzie","year":"2004","journal-title":"Nat. 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