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Three-dimensional structure of a flavivirus dumbbell RNA reveals molecular details of an RNA regulator of replication
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266583/ https://www.ncbi.nlm.nih.gov/pubmed/34133732 http://dx.doi.org/10.1093/nar/gkab462 |
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author | Akiyama, Benjamin M Graham, Monica E O′Donoghue, Zoe Beckham, J David Kieft, Jeffrey S |
author_facet | Akiyama, Benjamin M Graham, Monica E O′Donoghue, Zoe Beckham, J David Kieft, Jeffrey S |
author_sort | Akiyama, Benjamin M |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8266583 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-82665832021-07-09 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 Nucleic Acids Res Structural Biology 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. Oxford University Press 2021-06-16 /pmc/articles/PMC8266583/ /pubmed/34133732 http://dx.doi.org/10.1093/nar/gkab462 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Structural Biology Akiyama, Benjamin M Graham, Monica E O′Donoghue, Zoe Beckham, J David Kieft, Jeffrey S Three-dimensional structure of a flavivirus dumbbell RNA reveals molecular details of an RNA regulator of replication |
title | Three-dimensional structure of a flavivirus dumbbell RNA reveals molecular details of an RNA regulator of replication |
title_full | Three-dimensional structure of a flavivirus dumbbell RNA reveals molecular details of an RNA regulator of replication |
title_fullStr | Three-dimensional structure of a flavivirus dumbbell RNA reveals molecular details of an RNA regulator of replication |
title_full_unstemmed | Three-dimensional structure of a flavivirus dumbbell RNA reveals molecular details of an RNA regulator of replication |
title_short | Three-dimensional structure of a flavivirus dumbbell RNA reveals molecular details of an RNA regulator of replication |
title_sort | three-dimensional structure of a flavivirus dumbbell rna reveals molecular details of an rna regulator of replication |
topic | Structural Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266583/ https://www.ncbi.nlm.nih.gov/pubmed/34133732 http://dx.doi.org/10.1093/nar/gkab462 |
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