TY - JOUR
T1 - Dynamics of Human and Viral RNA Methylation during Zika Virus Infection
AU - Lichinchi, Gianluigi
AU - Zhao, Boxuan Simen
AU - Wu, Yinga
AU - Lu, Zhike
AU - Qin, Yue
AU - He, Chuan
AU - Rana, Tariq M.
N1 - We thank Steve Head and the staff of the Next Generation Sequencing core facility at UCSD for help with the HT-seq and data analysis. We thank Jason Dang for his help with preparation of the artwork and members of the T.M.R. lab for helpful discussions and advice. This work was supported in part by grants from the NIH. C.H. is an Investigator of the Howard Hughes Medical Institute (HHMI). B.S.Z. is an HHMI International Student Research Fellow.
PY - 2016/11/9
Y1 - 2016/11/9
N2 - 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.
AB - 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.
KW - 2′-O methylation
KW - mA methylation
KW - methyltransferases
KW - Zika virus
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U2 - 10.1016/j.chom.2016.10.002
DO - 10.1016/j.chom.2016.10.002
M3 - Article
C2 - 27773536
AN - SCOPUS:84994777582
SN - 1931-3128
VL - 20
SP - 666
EP - 673
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 5
ER -