@article{f947326038564fdab799fb1cb89138c6,
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.",
author = "Akiyama, {Benjamin M.} and Laurence, {Hannah M.} and Massey, {Aaron R.} and Costantino, {David A.} and Xuping Xie and Yujiao Yang and Shi, {Pei Yong} and Nix, {Jay C.} and Beckham, {J. David} and Kieft, {Jeffrey S.}",
note = "Funding Information: We thank the members of the Kieft lab for discussions; C. Musselman and M. Stone for critical reading of this manuscript; and R. Soto from the M. Garcia-Blanco and S. Bradrick laboratories for sharing their protocol for sfRNA blots. Supported by NIH fellowship F32GM117730 (B.M.A.); an HHMI Early Career Scientist award and NIH grants R35GM118070 and R01GM081346 (J.S.K.); a HHMI-Burroughs Wellcome Fund medical research fellowship (H.M.L.); University of Colorado School of Medicine and Department of Medicine institutional pilot funds (A.R.M. and J.D.B.); a postdoctoral fellowship from Novartis Institutes for BioMedical Research (X.X.); and a University of Texas Medical Branch startup award, a University of Texas STARs award, and NIH grant R01AI087856 (P.-Y.S.). The UC Denver X-ray Facility is supported by UC Cancer Center support grant P30CA046934 and NIH grant S10OD012033. The Advanced Light Source is supported by the Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under contract DE-AC02-05CH11231. The data presented in this manuscript are tabulated in the main paper and in the supplementary materials. Coordinates and structure factors have been deposited with PDB accession code 5TPY. Publisher Copyright: {\textcopyright} 2016, American Association for the Advancement of Science. All rights reserved.",
year = "2016",
month = dec,
day = "2",
doi = "10.1126/science.aah3963",
language = "English (US)",
volume = "354",
pages = "1148--1152",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6316",
}