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Dynamics of Human and Viral RNA Methylation during Zika Virus Infection

Title: Dynamics of Human and Viral RNA Methylation during Zika Virus Infection
Authors: Lichinchi, Gianluigi; Zhao, Boxuan Simen; Wu, Yinga; Lu, Zhike; Qin, Yue; He, Chuan; Rana, Tariq M
Source: Cell Host & Microbe, vol 20, iss 5
Publisher Information: eScholarship, University of California
Publication Year: 2016
Collection: University of California: eScholarship
Subject Terms: 3207 Medical Microbiology (for-2020); 32 Biomedical and Clinical Sciences (for-2020); 31 Biological Sciences (for-2020); Emerging Infectious Diseases (rcdc); Biodefense (rcdc); Vector-Borne Diseases (rcdc); Genetics (rcdc); Rare Diseases (rcdc); Infectious Diseases (rcdc); 2.1 Biological and endogenous factors (hrcs-rac); Infection (hrcs-hc); 3 Good Health and Well Being (sdg); AlkB Homolog 5; RNA Demethylase (mesh); Alpha-Ketoglutarate-Dependent Dioxygenase FTO (mesh); Cell Line (mesh); Host-Pathogen Interactions (mesh); Humans (mesh); Methylation (mesh); Methyltransferases (mesh); RNA Processing; Post-Transcriptional (mesh); RNA; Viral (mesh); Virus Replication (mesh); Zika Virus (mesh); 2′-O methylation; Zika virus; m(6)A methylation; methyltransferases
Subject Geographic: 666 - 673
Description: Infection with the flavivirus Zika (ZIKV) causes neurological, immunological, and developmental defects through incompletely understood mechanisms. We report that ZIKV infection affects viral and human RNAs by altering the topology and function of N6-adenosine methylation (m6A), a modification affecting RNA structure and function. m6A nucleosides are abundant in ZIKV RNA, with twelve m6A peaks identified across full-length ZIKV RNA. m6A in ZIKV RNA is controlled by host methyltransferases METTL3 and METTL14 and demethylases ALKBH5 and FTO, and knockdown of methyltransferases increases, while silencing demethylases decreases, ZIKV production. YTHDF family proteins, which regulate the stability of m6A-modified RNA, bind to ZIKV RNA, and their silencing increases ZIKV replication. Profiling of the m6A methylome of host mRNAs reveals that ZIKV infection alters m6A location in mRNAs, methylation motifs, and target genes modified by methyltransferases. Our results identify a mechanism by which ZIKV interacts with and alters host cell functions.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: unknown
Relation: qt097853nd; https://escholarship.org/uc/item/097853nd; https://escholarship.org/content/qt097853nd/qt097853nd.pdf
DOI: 10.1016/j.chom.2016.10.002
Availability: https://escholarship.org/uc/item/097853nd; https://escholarship.org/content/qt097853nd/qt097853nd.pdf; https://doi.org/10.1016/j.chom.2016.10.002
Rights: public
Accession Number: edsbas.4297A17F
Database: BASE