Tags

Type your tag names separated by a space and hit enter

Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization.
Elife. 2016 10 01; 5E

Abstract

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.

Authors+Show Affiliations

Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China. State Key Laboratory of Pathogen and Biosecurity, Beijing, China.Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China. State Key Laboratory of Pathogen and Biosecurity, Beijing, China.Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China. State Key Laboratory of Pathogen and Biosecurity, Beijing, China.Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China. State Key Laboratory of Pathogen and Biosecurity, Beijing, China.Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China.Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China.Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China.Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China. State Key Laboratory of Pathogen and Biosecurity, Beijing, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27692070

Citation

Liu, Zhong-Yu, et al. "Viral RNA Switch Mediates the Dynamic Control of Flavivirus Replicase Recruitment By Genome Cyclization." ELife, vol. 5, 2016.
Liu ZY, Li XF, Jiang T, et al. Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization. Elife. 2016;5.
Liu, Z. Y., Li, X. F., Jiang, T., Deng, Y. Q., Ye, Q., Zhao, H., Yu, J. Y., & Qin, C. F. (2016). Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization. ELife, 5. https://doi.org/10.7554/eLife.17636
Liu ZY, et al. Viral RNA Switch Mediates the Dynamic Control of Flavivirus Replicase Recruitment By Genome Cyclization. Elife. 2016 10 1;5 PubMed PMID: 27692070.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization. AU - Liu,Zhong-Yu, AU - Li,Xiao-Feng, AU - Jiang,Tao, AU - Deng,Yong-Qiang, AU - Ye,Qing, AU - Zhao,Hui, AU - Yu,Jiu-Yang, AU - Qin,Cheng-Feng, Y1 - 2016/10/01/ PY - 2016/05/09/received PY - 2016/09/30/accepted PY - 2016/10/4/pubmed PY - 2017/10/17/medline PY - 2016/10/4/entrez KW - biochemistry KW - cis-acting element KW - flavivirus KW - genome cyclization KW - infectious disease KW - microbiology KW - viral RNA structure KW - viral replicase recruitment KW - virus JF - eLife JO - Elife VL - 5 N2 - 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. SN - 2050-084X UR - https://www.unboundmedicine.com/medline/citation/27692070/Viral_RNA_switch_mediates_the_dynamic_control_of_flavivirus_replicase_recruitment_by_genome_cyclization_ L2 - https://doi.org/10.7554/eLife.17636 DB - PRIME DP - Unbound Medicine ER -