skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Zika virus produces noncoding RNAs using a multi-pseudoknot structure that confounds a cellular exonuclease

Abstract

The outbreak of Zika virus (ZIKV) and associated fetal microcephaly mandates efforts to understand the molecular processes of infection. Related flaviviruses produce noncoding subgenomic flaviviral RNAs (sfRNAs) that are linked to pathogenicity in fetal mice. These viruses make sfRNAs by co-opting a cellular exonuclease via structured RNAs called xrRNAs. We found that ZIKV-infected monkey and human epithelial cells, mouse neurons, and mosquito cells produce sfRNAs. The RNA structure that is responsible for ZIKV sfRNA production forms a complex fold that is likely found in many pathogenic flaviviruses. Mutations that disrupt the structure affect exonuclease resistance in vitro and sfRNA formation during infection. The complete ZIKV xrRNA structure clarifies the mechanism of exonuclease resistance and identifies features that may modulate function in diverse flaviviruses.

Authors:
 [1];  [2];  [3];  [1];  [4];  [4];  [4];  [5];  [3];  [6]
  1. Univ. of Colorado, Aurora, CO (United States). Denver School of Medicine, Dept. of Biochemistry and Molecular Genetics
  2. Univ. of Colorado, Aurora, CO (United States). Denver School of Medicine, Dept. of Biochemistry and Molecular Genetics; Univ. of Colorado, Aurora, CO (United States). Denver School of Medicine, Howard Hughes Medical Inst. (HHMI); Univ. of California, Davis, CA (United States). School of Veterinary Medicine
  3. Univ. of Colorado, Aurora, CO (United States). Denver School of Medicine, Dept. Medicine, Division of Infectious Diseases
  4. Univ. of Texas, Galveston, TX (United States). Medical Branch, Dept. of Biochemistry and Molecular Biology
  5. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS), Molecular Biology Consortium
  6. Univ. of Colorado, Aurora, CO (United States). Denver School of Medicine, Dept. of Biochemistry and Molecular Genetics; Univ. of Colorado, Aurora, CO (United States). Denver School of Medicine, RNA BioScience Initiative
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1411558
Grant/Contract Number:  
AC02-05CH11231; R35GM118070; R01GM081346; P30CA046934; S10OD012033
Resource Type:
Accepted Manuscript
Journal Name:
Science
Additional Journal Information:
Journal Volume: 354; Journal Issue: 6316; Journal ID: ISSN 0036-8075
Publisher:
AAAS
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Akiyama, Benjamin M., Laurence, Hannah M., Massey, Aaron R., Costantino, David A., Xie, Xuping, Yang, Yujiao, Shi, Pei-Yong -Y., Nix, Jay C., Beckham, J. David, and Kieft, Jeffrey S. Zika virus produces noncoding RNAs using a multi-pseudoknot structure that confounds a cellular exonuclease. United States: N. p., 2016. Web. doi:10.1126/science.aah3963.
Akiyama, Benjamin M., Laurence, Hannah M., Massey, Aaron R., Costantino, David A., Xie, Xuping, Yang, Yujiao, Shi, Pei-Yong -Y., Nix, Jay C., Beckham, J. David, & Kieft, Jeffrey S. Zika virus produces noncoding RNAs using a multi-pseudoknot structure that confounds a cellular exonuclease. United States. doi:10.1126/science.aah3963.
Akiyama, Benjamin M., Laurence, Hannah M., Massey, Aaron R., Costantino, David A., Xie, Xuping, Yang, Yujiao, Shi, Pei-Yong -Y., Nix, Jay C., Beckham, J. David, and Kieft, Jeffrey S. Thu . "Zika virus produces noncoding RNAs using a multi-pseudoknot structure that confounds a cellular exonuclease". United States. doi:10.1126/science.aah3963. https://www.osti.gov/servlets/purl/1411558.
@article{osti_1411558,
title = {Zika virus produces noncoding RNAs using a multi-pseudoknot structure that confounds a cellular exonuclease},
author = {Akiyama, Benjamin M. and Laurence, Hannah M. and Massey, Aaron R. and Costantino, David A. and Xie, Xuping and Yang, Yujiao and Shi, Pei-Yong -Y. and Nix, Jay C. and Beckham, J. David and Kieft, Jeffrey S.},
abstractNote = {The outbreak of Zika virus (ZIKV) and associated fetal microcephaly mandates efforts to understand the molecular processes of infection. Related flaviviruses produce noncoding subgenomic flaviviral RNAs (sfRNAs) that are linked to pathogenicity in fetal mice. These viruses make sfRNAs by co-opting a cellular exonuclease via structured RNAs called xrRNAs. We found that ZIKV-infected monkey and human epithelial cells, mouse neurons, and mosquito cells produce sfRNAs. The RNA structure that is responsible for ZIKV sfRNA production forms a complex fold that is likely found in many pathogenic flaviviruses. Mutations that disrupt the structure affect exonuclease resistance in vitro and sfRNA formation during infection. The complete ZIKV xrRNA structure clarifies the mechanism of exonuclease resistance and identifies features that may modulate function in diverse flaviviruses.},
doi = {10.1126/science.aah3963},
journal = {Science},
number = 6316,
volume = 354,
place = {United States},
year = {2016},
month = {11}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 33 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Electrostatics of nanosystems: Application to microtubules and the ribosome
journal, August 2001

  • Baker, N. A.; Sept, D.; Joseph, S.
  • Proceedings of the National Academy of Sciences, Vol. 98, Issue 18, p. 10037-10041
  • DOI: 10.1073/pnas.181342398

Coot model-building tools for molecular graphics
journal, November 2004

  • Emsley, Paul; Cowtan, Kevin
  • Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
  • DOI: 10.1107/S0907444904019158

PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

Scaling and assessment of data quality
journal, December 2005

  • Evans, Philip
  • Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 1, p. 72-82
  • DOI: 10.1107/S0907444905036693