1. Biochemistry and Chemical Biology
  2. Microbiology and Infectious Disease
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Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization

  1. Zhong-Yu Liu
  2. Xiao-Feng Li
  3. Tao Jiang
  4. Yong-Qiang Deng
  5. Qing Ye
  6. Hui Zhao
  7. Jiu-Yang Yu
  8. Cheng-Feng Qin  Is a corresponding author
  1. Beijing Institute of Microbiology and Epidemiology, China
Research Article
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Cite this article as: eLife 2016;5:e17636 doi: 10.7554/eLife.17636

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.

Article and author information

Author details

  1. Zhong-Yu Liu

    Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Xiao-Feng Li

    Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Tao Jiang

    Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Yong-Qiang Deng

    Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Qing Ye

    Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Hui Zhao

    Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Jiu-Yang Yu

    Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Cheng-Feng Qin

    Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China
    For correspondence
    qincf@bmi.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0632-2807

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.

Reviewing Editor

  1. Jeffrey S Kieft, University of Colorado Denver School of Medicine, United States

Publication history

  1. Received: May 9, 2016
  2. Accepted: September 30, 2016
  3. Accepted Manuscript published: October 1, 2016 (version 1)
  4. Version of Record published: November 8, 2016 (version 2)

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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