Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization
- Beijing Institute of Microbiology and Epidemiology, China
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.
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Funding
National Natural Science Foundation of China (31270196)
- Cheng-Feng Qin
National Natural Science Foundation of China (31000083)
- Xiao-Feng Li
National Natural Science Foundation of China (30972613)
- Cheng-Feng Qin
National Natural Science Foundation of China (National Basic Research Program of China, 2012CB518904)
- Cheng-Feng Qin
National Natural Science Foundation of China (Excellent Young Scientist Program, 81522025)
- Cheng-Feng Qin
Academy of Medical Sciences (Newton Advanced Fellowship, 81661130162)
- Cheng-Feng Qin
National Key Research and Development Project of China (2016YFD0500304)
- Cheng-Feng Qin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2016, Liu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization
eLife 5:e17636.
https://doi.org/10.7554/eLife.17636
