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

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

Akiyama BM1Laurence HM1,2,3Massey AR4Costantino DA1Xie X5Yang Y5Shi PY5Nix JC6Beckham JD4Kieft JS7,8.

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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.

Copyright © 2016, American Association for the Advancement of Science.

PMID:27934765  PMCID:PMC5476369  DOI:10.1126/science.aah3963




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