Cargando…

Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization

Viral replicase recruitment and long-range RNA interactions are essential for RNA virus replication, yet the mechanism of their interplay remains elusive. Flaviviruses include numerous important human pathogens, e.g., dengue virus (DENV) and Zika virus (ZIKV). Here, we revealed a highly conserved, c...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Zhong-Yu, Li, Xiao-Feng, Jiang, Tao, Deng, Yong-Qiang, Ye, Qing, Zhao, Hui, Yu, Jiu-Yang, Qin, Cheng-Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101012/
https://www.ncbi.nlm.nih.gov/pubmed/27692070
http://dx.doi.org/10.7554/eLife.17636
_version_ 1782466235113406464
author Liu, Zhong-Yu
Li, Xiao-Feng
Jiang, Tao
Deng, Yong-Qiang
Ye, Qing
Zhao, Hui
Yu, Jiu-Yang
Qin, Cheng-Feng
author_facet Liu, Zhong-Yu
Li, Xiao-Feng
Jiang, Tao
Deng, Yong-Qiang
Ye, Qing
Zhao, Hui
Yu, Jiu-Yang
Qin, Cheng-Feng
author_sort Liu, Zhong-Yu
collection PubMed
description Viral replicase recruitment and long-range RNA interactions are essential for RNA virus replication, yet the mechanism of their interplay remains elusive. Flaviviruses include numerous important human pathogens, e.g., dengue virus (DENV) and Zika virus (ZIKV). Here, we revealed a highly conserved, conformation-tunable cis-acting element named 5′-UAR-flanking stem (UFS) in the flavivirus genomic 5′ terminus. We demonstrated that the UFS was critical for efficient NS5 recruitment and viral RNA synthesis in different flaviviruses. Interestingly, stabilization of the DENV UFS impaired both genome cyclization and vRNA replication. Moreover, the UFS unwound in response to genome cyclization, leading to the decreased affinity of NS5 for the viral 5′ end. Thus, we propose that the UFS is switched by genome cyclization to regulate dynamic RdRp binding for vRNA replication. This study demonstrates that the UFS enables communication between flavivirus genome cyclization and RdRp recruitment, highlighting the presence of switch-like mechanisms among RNA viruses. DOI: http://dx.doi.org/10.7554/eLife.17636.001
format Online
Article
Text
id pubmed-5101012
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-51010122016-11-10 Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization Liu, Zhong-Yu Li, Xiao-Feng Jiang, Tao Deng, Yong-Qiang Ye, Qing Zhao, Hui Yu, Jiu-Yang Qin, Cheng-Feng eLife Biochemistry Viral replicase recruitment and long-range RNA interactions are essential for RNA virus replication, yet the mechanism of their interplay remains elusive. Flaviviruses include numerous important human pathogens, e.g., dengue virus (DENV) and Zika virus (ZIKV). Here, we revealed a highly conserved, conformation-tunable cis-acting element named 5′-UAR-flanking stem (UFS) in the flavivirus genomic 5′ terminus. We demonstrated that the UFS was critical for efficient NS5 recruitment and viral RNA synthesis in different flaviviruses. Interestingly, stabilization of the DENV UFS impaired both genome cyclization and vRNA replication. Moreover, the UFS unwound in response to genome cyclization, leading to the decreased affinity of NS5 for the viral 5′ end. Thus, we propose that the UFS is switched by genome cyclization to regulate dynamic RdRp binding for vRNA replication. This study demonstrates that the UFS enables communication between flavivirus genome cyclization and RdRp recruitment, highlighting the presence of switch-like mechanisms among RNA viruses. DOI: http://dx.doi.org/10.7554/eLife.17636.001 eLife Sciences Publications, Ltd 2016-10-01 /pmc/articles/PMC5101012/ /pubmed/27692070 http://dx.doi.org/10.7554/eLife.17636 Text en © 2016, Liu et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biochemistry
Liu, Zhong-Yu
Li, Xiao-Feng
Jiang, Tao
Deng, Yong-Qiang
Ye, Qing
Zhao, Hui
Yu, Jiu-Yang
Qin, Cheng-Feng
Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization
title Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization
title_full Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization
title_fullStr Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization
title_full_unstemmed Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization
title_short Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization
title_sort viral rna switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization
topic Biochemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101012/
https://www.ncbi.nlm.nih.gov/pubmed/27692070
http://dx.doi.org/10.7554/eLife.17636
work_keys_str_mv AT liuzhongyu viralrnaswitchmediatesthedynamiccontrolofflavivirusreplicaserecruitmentbygenomecyclization
AT lixiaofeng viralrnaswitchmediatesthedynamiccontrolofflavivirusreplicaserecruitmentbygenomecyclization
AT jiangtao viralrnaswitchmediatesthedynamiccontrolofflavivirusreplicaserecruitmentbygenomecyclization
AT dengyongqiang viralrnaswitchmediatesthedynamiccontrolofflavivirusreplicaserecruitmentbygenomecyclization
AT yeqing viralrnaswitchmediatesthedynamiccontrolofflavivirusreplicaserecruitmentbygenomecyclization
AT zhaohui viralrnaswitchmediatesthedynamiccontrolofflavivirusreplicaserecruitmentbygenomecyclization
AT yujiuyang viralrnaswitchmediatesthedynamiccontrolofflavivirusreplicaserecruitmentbygenomecyclization
AT qinchengfeng viralrnaswitchmediatesthedynamiccontrolofflavivirusreplicaserecruitmentbygenomecyclization