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

Journal Article · · Science
 [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

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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-05CH11231; R35GM118070; R01GM081346; P30CA046934; S10OD012033
OSTI ID:
1411558
Journal Information:
Science, Vol. 354, Issue 6316; ISSN 0036-8075
Publisher:
AAASCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 158 works
Citation information provided by
Web of Science

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Functional RNA Structures in the 3’UTR of Tick-Borne, Insect-Specific and No-Known-Vector Flaviviruses journal March 2019
Dimerization confers increased stability to nucleases in 5′ halves from glycine and glutamic acid tRNAs journal June 2018
Investigational drugs for the treatment of Zika virus infection: a preclinical and clinical update journal November 2018
Zika virus has oncolytic activity against glioblastoma stem cells journal September 2017
Mechanism and structural diversity of exoribonuclease-resistant RNA structures in flaviviral RNAs journal January 2018
The conserved stem-loop II structure at the 3' untranslated region of Japanese encephalitis virus genome is required for the formation of subgenomic flaviviral RNA journal July 2018
Zika virus: An emerging flavivirus journal February 2017
Evolution of Two Major Zika Virus Lineages: Implications for Pathology, Immune Response, and Vaccine Development journal July 2018
Structure mapping of dengue and Zika viruses reveals functional long-range interactions journal March 2019
Evolution of Subgenomic RNA Shapes Dengue Virus Adaptation and Epidemiological Fitness text January 2019
Dengue subgenomic flaviviral RNA disrupts immunity in mosquito salivary glands to increase virus transmission journal July 2017
Functional RNA Structures in the 3'UTR of Tick-Borne, Insect-Specific and No-Known-Vector Flaviviruses journal March 2019
The evolution of Zika virus from Asia to the Americas journal January 2019
Blind prediction of noncanonical RNA structure at atomic accuracy journal May 2018
ScanFold: an approach for genome-wide discovery of local RNA structural elements—applications to Zika virus and HIV journal January 2018
Human T cell leukemia virus type 1 and Zika virus: tale of two reemerging viruses with neuropathological sequelae of public health concern journal January 2019
Zika Virus Hijacks Stress Granule Proteins and Modulates the Host Stress Response journal June 2017
Suggested mechanisms for Zika virus causing microcephaly: what do the genomes tell us? journal December 2017
Musashi binding elements in Zika and related Flavivirus 3’UTRs: A comparative study in silico journal March 2019
Circularization of flavivirus genomic RNA inhibits de novo translation initiation. text January 2019
Viral Determinants and Vector Competence of Zika Virus Transmission journal May 2018
Long non‐coding subgenomic flavivirus RNAs have extended 3D structures and are flexible in solution journal September 2019
Characterization of cis -Acting RNA Elements of Zika Virus by Using a Self-Splicing Ribozyme-Dependent Infectious Clone journal August 2017
Circularization of flavivirus genomic RNA inhibits de novo translation initiation journal August 2019
Musashi binding elements in Zika and related Flavivirus 3′UTRs: A comparative study in silico journal May 2019
The exoribonuclease Xrn1 is a post-transcriptional negative regulator of autophagy journal January 2018
A Zika virus from America is more efficiently transmitted than an Asian virus by Aedes aegypti mosquitoes from Asia journal April 2017
Wolbachia-mediated virus blocking in mosquito cells is dependent on XRN1-mediated viral RNA degradation and influenced by viral replication rate journal March 2018
How does Zika virus cause microcephaly? journal May 2017
The 5′ and 3′ Untranslated Regions of the Flaviviral Genome journal June 2017
COMRADES determines in vivo RNA structures and interactions. text January 2018
FARFAR2: Improved de novo Rosetta prediction of complex global RNA folds journal September 2019
Evolution of Subgenomic RNA Shapes Dengue Virus Adaptation and Epidemiological Fitness journal June 2019
In vitro and in vivo models for studying Zika virus biology journal December 2018
MicroRNAs 145 and 148a Are Upregulated During Congenital Zika Virus Infection journal January 2019
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Early Events in Japanese Encephalitis Virus Infection: Viral Entry journal August 2018
Evolution of Subgenomic RNA Shapes Dengue Virus Adaptation and Epidemiological Fitness journal January 2018
Pervasiveness of exoribonuclease-resistant RNAs in plant viruses suggests new roles for these conserved RNA structures journal October 2018
Structure and function of cis ‐acting RNA elements of flavivirus journal November 2019
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Zika Virus: What Have We Learnt Since the Start of the Recent Epidemic? journal August 2017
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