N6-methyladenosine (m6A) recruits and repels proteins to regulate mRNA homeostasis

被引：520

作者：

Edupuganti, Raghu R. ^{[1
]}

Geiger, Simon ^{[2
]}

Lindeboom, Rik G. H. ^{[1
]}

Shi, Hailing ^{[3
,4
]}

Hsu, Phillip J. ^{[3
,4
]}

Lu, Zhike ^{[3
,4
]}

Wang, Shuang-Yin ^{[1
]}

Baltissen, Marijke P. A. ^{[1
]}

Jansen, Pascal W. T. C. ^{[1
]}

Rossa, Martin ^{[2
]}

Mueller, Markus ^{[2
]}

Stunnenberg, Hendrik G. ^{[1
]}

He, Chuan ^{[3
,4
]}

Carell, Thomas ^{[2
]}

Vermeulen, Michiel ^{[1
]}

机构：

[1] Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Mol Biol, Fac Sci, Nijmegen, Netherlands

[2] Ludwig Maximilians Univ Munchen, Ctr Integrated Prot Sci, Fak Chem & Pharm, Munich, Germany

[3] Univ Chicago, Howard Hughes Med Inst, Dept Chem, Dept Biochem & Mol Biol, 5841 S Maryland Ave, Chicago, IL 60637 USA

[4] Univ Chicago, Howard Hughes Med Inst, Inst Biophys Dynam, 5841 S Maryland Ave, Chicago, IL 60637 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2017年 / 24卷 / 10期

关键词：

EMBRYONIC STEM-CELLS; FRAGILE-X-SYNDROME; STRESS GRANULES; NUCLEAR-RNA; GENE-EXPRESSION; METHYLATION; TRANSLATION; PROTEOME; N6-METHYLADENOSINE; METHYLTRANSFERASE;

D O I：

10.1038/nsmb.3462

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

RNA modifications are integral to the regulation of RNA metabolism. One abundant mRNA modification is N-6-methyladenosine (m(6)A), which affects various aspects of RNA metabolism, including splicing, translation and degradation. Current knowledge about the proteins recruited to m(6)A to carry out these molecular processes is still limited. Here we describe comprehensive and systematic mass-spectrometry-based screening of m(6)A interactors in various cell types and sequence contexts. Among the main findings, we identified G3BP1 as a protein that is repelled by m(6)A and positively regulates mRNA stability in an m(6)A-regulated manner. Furthermore, we identified FMR1 as a sequence-context-dependent m(6)A reader, thus revealing a connection between an mRNA modification and an autism spectrum disorder. Collectively, our data represent a rich resource and shed further light on the complex interplay among m(6)A, m(6)A interactors and mRNA homeostasis.

引用

页码：870 / +

页数：12

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