The m6A methylome of SARS-CoV-2 in host cells

被引：119

作者：

Liu, Jun'e ^{[1
,2
,3
]}

Xu, Yan-Peng ^{[4
]}

Li, Kai ^{[1
,5
,6
]}

Ye, Qing ^{[4
]}

Zhou, Hang-Yu ^{[7
]}

Sun, Hanxiao ^{[1
]}

Li, Xiaoyu ^{[1
]}

Yu, Liu ^{[4
]}

Deng, Yong-Qiang ^{[4
]}

Li, Rui-Ting ^{[4
]}

Cheng, Meng-Li ^{[4
]}

He, Bo ^{[5
,6
]}

Zhou, Jia ^{[4
]}

Li, Xiao-Feng ^{[4
]}

Wu, Aiping ^{[7
]}

Yi, Chengqi ^{[1
,6
,8
,9
]}

Qin, Cheng-Feng ^{[4
]}

机构：

[1] Peking Univ, Sch Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China

[2] Peking Univ, Beijing Adv Innovat Ctr Genom ICG, Beijing 100871, Peoples R China

[3] Minist Educ, Key Lab Cell Proliferat & Differentiat, Biomed Pioneering Innovat Ctr, Beijing 100871, Peoples R China

[4] Acad Mil Med Sci, Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing 100071, Peoples R China

[5] Peking Univ, Acad Adv Interdisciplinary Studies, Beijing 100871, Peoples R China

[6] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China

[7] Chinese Acad Med Sci & Peking Union Med Coll, Suzhou Inst Syst Med, Suzhou 215000, Jiangsu, Peoples R China

[8] Peking Univ, Coll Chem & Mol Engn, Dept Chem Biol, Beijing 100871, Peoples R China

[9] Peking Univ, Coll Chem & Mol Engn, Synthet & Funct Biomol Ctr, Beijing 100871, Peoples R China

来源：

CELL RESEARCH | 2021年 / 31卷 / 04期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

MESSENGER-RNA; SEQUENCE SPECIFICITY; METHYLATION; N6-METHYLADENOSINE; METHYLTRANSFERASE; VISUALIZATION; PURIFICATION; DEMETHYLASE; DYNAMICS; NUCLEAR;

D O I：

10.1038/s41422-020-00465-7

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The newly identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a global health emergency because of its rapid spread and high mortality. The molecular mechanism of interaction between host and viral genomic RNA is yet unclear. We demonstrate herein that SARS-CoV-2 genomic RNA, as well as the negative-sense RNA, is dynamically N-6-methyladenosine (m(6)A)-modified in human and monkey cells. Combined RIP-seq and miCLIP analyses identified a total of 8 m(6)A sites at single-base resolution in the genome. Especially, epidemic strains with mutations at these identified m(6)A sites have emerged worldwide, and formed a unique cluster in the US as indicated by phylogenetic analysis. Further functional experiments showed that m(6)A methylation negatively regulates SARS-CoV-2 infection. SARS-CoV-2 infection also triggered a global increase in host m(6)A methylome, exhibiting altered localization and motifs of m(6)A methylation in mRNAs. Altogether, our results identify m(6)A as a dynamic epitranscriptomic mark mediating the virus-host interaction.

引用

页码：404 / 414

页数：11

共 62 条

[11]

Dominissini Dan, 2018, Nat Struct Mol Biol, DOI 10.1038/s41594-018-0140-7

[12] Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq [J].

Dominissini, Dan ;

Moshitch-Moshkovitz, Sharon ;

Schwartz, Schraga ;

Salmon-Divon, Mali ;

Ungar, Lior ;

Osenberg, Sivan ;

Cesarkas, Karen ;

Jacob-Hirsch, Jasmine ;

Amariglio, Ninette ;

Kupiec, Martin ;

Sorek, Rotem ;

Rechavi, Gideon .

NATURE, 2012, 485 (7397) :201-U84

[13] RNA modifications: what have we learned and where are we headed? [J].

Frye, Michaela ;

Jaffrey, Samie R. ;

Pan, Tao ;

Rechavi, Gideon ;

Suzuki, Tsutomu .

NATURE REVIEWS GENETICS, 2016, 17 (06) :365-372

[14] Gene expression regulation mediated through reversible m6A RNA methylation [J].

Fu, Ye ;

Dominissini, Dan ;

Rechavi, Gideon ;

He, Chuan .

NATURE REVIEWS GENETICS, 2014, 15 (05) :293-306

[15]

Global Initiative on Sharing All Influenza Data (GISAID), CLADE LINEAGE NOMENC

[16] N6-Methyladenosine in Flaviviridae Viral RNA Genomes Regulates Infection [J].

Gokhale, Nandan S. ;

McIntyre, Alexa B. R. ;

McFadden, Michael J. ;

Roder, Allison E. ;

Kennedy, Edward M. ;

Gandara, Jorge A. ;

Hopcraft, Sharon E. ;

Quicke, Kendra M. ;

Vazquez, Christine ;

Willer, Jason ;

Ilkayeva, Olga R. ;

Law, Brittany A. ;

Holley, Christopher L. ;

Garcia-Blanco, Mariano A. ;

Evans, Matthew J. ;

Suthar, Mehul S. ;

Bradrick, Shelton S. ;

Mason, Christopher E. ;

Horner, Stacy M. .

CELL HOST & MICROBE, 2016, 20 (05) :654-665

[17] SEQUENCE SPECIFICITY OF THE HUMAN MESSENGER-RNA N6-ADENOSINE METHYLASE INVITRO [J].

HARPER, JE ;

MICELI, SM ;

ROBERTS, RJ ;

MANLEY, JL .

NUCLEIC ACIDS RESEARCH, 1990, 18 (19) :5735-5741

[18] Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources [J].

Huang, Da Wei ;

Sherman, Brad T. ;

Lempicki, Richard A. .

NATURE PROTOCOLS, 2009, 4 (01) :44-57

[19]

Jia GF, 2011, NAT CHEM BIOL, V7, P885, DOI [10.1038/NCHEMBIO.687, 10.1038/nchembio.687]

[20] PRECISE LOCALIZATION OF M6A IN ROUS-SARCOMA VIRUS-RNA REVEALS CLUSTERING OF METHYLATION SITES - IMPLICATIONS FOR RNA PROCESSING [J].

KANE, SE ;

BEEMON, K .

MOLECULAR AND CELLULAR BIOLOGY, 1985, 5 (09) :2298-2306

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