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:
-
- 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, 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
- Univ. of Colorado, Aurora, CO (United States). Denver School of Medicine, Dept. Medicine, Division of Infectious Diseases
- Univ. of Texas, Galveston, TX (United States). Medical Branch, Dept. of Biochemistry and Molecular Biology
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS), Molecular Biology Consortium
- 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 Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- 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. https://doi.org/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. https://doi.org/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 = {Thu Nov 10 00:00:00 EST 2016},
month = {Thu Nov 10 00:00:00 EST 2016}
}
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