Dynamics of the human and viral m 6 A RNA methylomes during HIV-1 infection of T cells
Gianluigi Lichinchi,Gianluigi Lichinchi,Shang Gao,Yogesh Saletore,Gwendolyn Gonzalez,Vikas Bansal,Yinsheng Wang,Christopher E. Mason,Tariq M. Rana,Tariq M. Rana +9 more
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TLDR
It is shown that viral infection triggers a massive increase in m6A in both host and viral mRNAs, which identifies a new mechanism for the control of HIV-1 replication and its interaction with the host immune system.Abstract:
N6-methyladenosine (m6A) is the most prevalent internal modification of eukaryotic mRNA. Very little is known of the function of m6A in the immune system or its role in host–pathogen interactions. Here, we investigate the topology, dynamics and bidirectional influences of the viral–host RNA methylomes during HIV-1 infection of human CD4 T cells. We show that viral infection triggers a massive increase in m6A in both host and viral mRNAs. In HIV-1 mRNA, we identified 14 methylation peaks in coding and noncoding regions, splicing junctions and splicing regulatory sequences. We also identified a set of 56 human gene transcripts that were uniquely methylated in HIV-1-infected T cells and were enriched for functions in viral gene expression. The functional relevance of m6A for viral replication was demonstrated by silencing of the m6A writer or the eraser enzymes, which decreased or increased HIV-1 replication, respectively. Furthermore, methylation of two conserved adenosines in the stem loop II region of HIV-1 Rev response element (RRE) RNA enhanced binding of HIV-1 Rev protein to the RRE in vivo and influenced nuclear export of RNA. Our results identify a new mechanism for the control of HIV-1 replication and its interaction with the host immune system. Infection with HIV-1 triggers an increase in N6-methyladenosine (m6A) modification of both viral and host mRNAs, which impacts viral replication and nuclear export of viral RNA.read more
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Journal ArticleDOI
Post-transcriptional gene regulation by mRNA modifications
TL;DR: N6-adenosine methylation directs mRNAs to distinct fates by grouping them for differential processing, translation and decay in processes such as cell differentiation, embryonic development and stress responses.
Journal ArticleDOI
Reading, writing and erasing mRNA methylation.
TL;DR: New and emerging methods to characterize and quantify the epitranscriptome are reviewed, and new concepts — in some cases, controversies — are discussed regarding the authors' understanding of the mechanisms and functions of m6A readers, writers and erasers are discussed.
Journal ArticleDOI
YTHDC1 mediates nuclear export of N 6 -methyladenosine methylated mRNAs.
Ian A Roundtree,Guan-Zheng Luo,Guan-Zheng Luo,Zijie Zhang,Zijie Zhang,Xiao Wang,Xiao Wang,Tao Zhou,Yiquang Cui,Jiahao Sha,Xingxu Huang,Laura Guerrero,Laura Guerrero,Phil Xie,Phil Xie,Emily He,Emily He,Bin Shen,Chuan He,Chuan He +19 more
TL;DR: It is shown that the m6A-binding protein YTHDC1 mediates export of methylated mRNA from the nucleus to the cytoplasm in HeLa cells, and supports an emerging paradigm of m 6A as a distinct biochemical entity for selective processing and metabolism of mammalian mRNAs.
Journal ArticleDOI
METTL3 promote tumor proliferation of bladder cancer by accelerating pri-miR221/222 maturation in m6A-dependent manner
Jie Han,Jingzi Wang,Xiao Yang,Hao Yu,Rui Zhou,Hongcheng Lu,Wenbo Yuan,Jian-chen Lu,Zijian Zhou,Qiang Lu,Ji-Fu Wei,Haiwei Yang +11 more
TL;DR: This is the first comprehensive study that METTL3 affected the tumor formation by the regulation the m6A modification in non-coding RNAs, which might provide fresh insights into bladder cancer therapy.
Journal ArticleDOI
Reading m6A in the Transcriptome: m6A-Binding Proteins
TL;DR: The mechanisms by which YTH domain-containing proteins bind m6A and influence the fate of m6Methyladenosine-containing RNA in mammalian cells are described.
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Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq
Dan Dominissini,Sharon Moshitch-Moshkovitz,Schraga Schwartz,Schraga Schwartz,Mali Salmon-Divon,Lior Ungar,Sivan Osenberg,Sivan Osenberg,Karen Cesarkas,Jasmine Jacob-Hirsch,Ninette Amariglio,Martin Kupiec,Rotem Sorek,Gideon Rechavi,Gideon Rechavi +14 more
TL;DR: The findings suggest that RNA decoration by m6A has a fundamental role in regulation of gene expression, and a subset of stimulus-dependent, dynamically modulated sites is identified.
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