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Science. 2016 Dec 2;354(6316):1148-1152. Epub 2016 Nov 10.

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

Author information

1
Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA.
2
Howard Hughes Medical Institute (HHMI), University of Colorado Denver School of Medicine, Aurora, CO 80045, USA.
3
School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
4
Department of Medicine, Division of Infectious Diseases, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA.
5
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
6
Molecular Biology Consortium, Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
7
Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA. jeffrey.kieft@ucdenver.edu.
8
RNA BioScience Initiative, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA.

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.

PMID:
27934765
PMCID:
PMC5476369
DOI:
10.1126/science.aah3963
[Indexed for MEDLINE]
Free PMC Article

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