ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility

被引：2894

作者：

Zheng, Guanqun ^{[1
]}

Dahl, John Arne ^{[3
]}

Niu, Yamei ^{[2
]}

Fedorcsak, Peter ^{[4
]}

Huang, Chun-Min ^{[2
]}

Li, Charles J. ^{[1
]}

Vagbo, Cathrine B. ^{[6
]}

Shi, Yue ^{[2
,7
]}

Wang, Wen-Ling ^{[2
,7
]}

Song, Shu-Hui ^{[5
]}

Lu, Zhike ^{[1
]}

Bosmans, Ralph P. G. ^{[1
]}

Dai, Qing ^{[1
]}

Hao, Ya-Juan ^{[2
,7
]}

Yang, Xin ^{[2
,7
]}

Zhao, Wen-Ming ^{[5
]}

Tong, Wei-Min ^{[8
,9
,10
]}

Wang, Xiu-Jie ^{[11
]}

Bogdan, Florian ^{[3
]}

Furu, Kari ^{[3
]}

Fu, Ye ^{[1
]}

Jia, Guifang ^{[1
]}

Zhao, Xu ^{[2
,7
]}

Liu, Jun ^{[12
,13
]}

Krokan, Hans E. ^{[6
]}

Klungland, Arne ^{[3
]}

Yang, Yun-Gui ^{[2
,7
]}

He, Chuan ^{[1
]}

机构：

[1] Univ Chicago, Inst Biophys Dynam, Dept Chem, Chicago, IL 60637 USA

[2] Chinese Acad Sci, Beijing Inst Genom, Dis Genom & Individualized Med Lab, Genome Struct & Stabil Grp,BIG CAS OSLO Genome Re, Beijing 100029, Peoples R China

[3] Oslo Univ Hosp, BIG CAS OSLO Genome Res Cooperat, Inst Med Microbiol, Ctr Mol Biol & Neurosci, N-0027 Oslo, Norway

[4] Oslo Univ Hosp, Dept Gynecol, Rikshosp, N-0027 Oslo, Norway

[5] Chinese Acad Sci, Beijing Inst Genom, Core Genom Facil, Beijing 100029, Peoples R China

[6] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, N-7489 Trondheim, Norway

[7] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[8] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Pathol, Beijing 100005, Peoples R China

[9] Chinese Acad Med Sci, Inst Basic Med Sci, Ctr Expt Anim Res, Beijing 100005, Peoples R China

[10] Peking Union Med Coll, Beijing 100005, Peoples R China

[11] Chinese Acad Sci, Inst Genet & Dev Biol, Beijing 100101, Peoples R China

[12] Peking Univ, Coll Chem & Mol Engn, Beijing 100871, Peoples R China

[13] Peking Univ, Synthet & Funct Biomol Ctr, Beijing 100871, Peoples R China

来源：

MOLECULAR CELL | 2013年 / 49卷 / 01期

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

MESSENGER-RNA; GENE-EXPRESSION; FTO GENE; OXIDATIVE DEMETHYLATION; TRANSLATION INITIATION; HISTONE DEMETHYLATION; NUCLEAR-RNA; DNA; ASSOCIATION; N6-METHYLADENOSINE;

D O I：

10.1016/j.molcel.2012.10.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

N-6-methyladenosine (m(6)A) is the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Here we report ALKBH5 as another mammalian demethylase that oxidatively reverses m(6)A in mRNA in vitro and in vivo. This demethylation activity of ALKBH5 significantly affects mRNA export and RNA metabolism as well as the assembly of mRNA processing factors in nuclear speckles. Alkbh5-deficient male mice have increased m(6)A in mRNA and are characterized by impaired fertility resulting from apoptosis that affects meiotic metaphase-stage spermatocytes. In accordance with this defect, we have identified in mouse testes 1,551 differentially expressed genes that cover broad functional categories and include spermatogenesis-related mRNAs involved in the p53 functional interaction network. The discovery of this RNA demethylase strongly suggests that the reversible m(6)A modification has fundamental and broad functions in mammalian cells.

引用

页码：18 / 29

页数：12

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