气候变化领域集成服务门户(CCPortal): Widespread remodeling of the m6A RNA-modification landscape by a viral regulator of RNA processing and export

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DOI	10.1073/pnas.2104805118
	Widespread remodeling of the m6A RNA-modification landscape by a viral regulator of RNA processing and export
	Srinivas K.P.; Depledge D.P.; Abebe J.S.; Rice S.A.; Mohr I.; Wilson A.C.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:30
英文摘要	N6-methyladenosine (m6A) is the most abundant internal messenger RNA (mRNA) modification, contributing to the processing, stability, and function of methylated RNAs. Methylation occurs in the nucleus during pre-mRNA synthesis and requires a core methyltransferase complex consisting of METTL3, METTL14, and WTAP. During herpes simplex virus (HSV-1) infection, cellular gene expression is profoundly suppressed, allowing the virus to monopolize the host transcription and translation apparatus and antagonize antiviral responses. The extent to which HSV-1 uses or manipulates the m6A pathway is not known. Here, we show that, in primary fibroblasts, HSV-1 orchestrates a striking redistribution of the nuclear m6A machinery that progresses through the infection cycle. METTL3 and METTL14 are dispersed into the cytoplasm, whereas WTAP remains nuclear. Other regulatory subunits of the methyltransferase complex, along with the nuclear m6A-modified RNA binding protein YTHDC1 and nuclear demethylase ALKBH5, are similarly redistributed. These changes require ICP27, a viral regulator of host mRNA processing that mediates the nucleocytoplasmic export of viral late mRNAs. Viral gene expression is initially reduced by small interfering RNA (siRNA)-mediated inactivation of the m6A methyltransferase but becomes less impacted as the infection advances. Redistribution of the nuclear m6A machinery is accompanied by a wide-scale reduction in the installation of m6A and other RNA modifications on both host and viral mRNAs. These results reveal a far-reaching mechanism by which HSV-1 subverts host gene expression to favor viral replication. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Direct RNA sequencing; Herpes simplex virus; N6-methyladenosine; Nanopore; RNA modification
语种	英语
scopus关键词	6 n methyladenosine; messenger RNA; RNA binding protein; small interfering RNA; virus RNA; 6-methyladenine mRNA methyltransferase; cell cycle protein; messenger RNA; methyltransferase; METTL14 protein, human; METTL3 protein, human; RNA splicing factor; WTAP protein, human; ALKBH5 gene; Article; controlled study; cytoplasm; DNA modification; fibroblast; gene expression; gene function; herpes virus infection; host cell; Human alphaherpesvirus 1; ICP27 gene; landscape; m6A gene; METTL14 gene; METTL3 gene; molecular genetic phenomena and functions; nonhuman; RNA processing; virus gene; WTAP gene; YTHDC1 gene; animal; cell line; Chlorocebus aethiops; gene expression regulation; genetics; human; metabolism; physiology; procedures; RNA interference; RNA processing; Vero cell line; virus replication; Animals; Cell Cycle Proteins; Cell Line; Chlorocebus aethiops; Gene Expression Regulation, Enzymologic; Herpesvirus 1, Human; Humans; Methyltransferases; RNA Interference; RNA Processing, Post-Transcriptional; RNA Splicing Factors; RNA, Messenger; RNA-Seq; Vero Cells; Virus Replication
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251112
作者单位	Department of Microbiology, New York University, Grossman School of Medicine, New York University, New York, NY 10016, United States; Department of Medicine, New York University, Grossman School of Medicine, New York University, New York, NY 10016, United States; Department of Microbiology, University of Minnesota Medical School, University of Minnesota, Minneapolis, MN 55455, United States
推荐引用方式 GB/T 7714	Srinivas K.P.,Depledge D.P.,Abebe J.S.,et al. Widespread remodeling of the m6A RNA-modification landscape by a viral regulator of RNA processing and export[J],2021,118(30).
APA	Srinivas K.P.,Depledge D.P.,Abebe J.S.,Rice S.A.,Mohr I.,&Wilson A.C..(2021).Widespread remodeling of the m6A RNA-modification landscape by a viral regulator of RNA processing and export.Proceedings of the National Academy of Sciences of the United States of America,118(30).
MLA	Srinivas K.P.,et al."Widespread remodeling of the m6A RNA-modification landscape by a viral regulator of RNA processing and export".Proceedings of the National Academy of Sciences of the United States of America 118.30(2021).