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

被引：2748

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

共 50 条

[41] RNA demethylase ALKBH5 promotes tumorigenesis of t (8;21) acute myeloid leukemia via ITPA m6A modification
Li, Ran
Wu, Xiaolu
Xue, Kai
Feng, Dandan
Li, Jianyong
Li, Junmin
BIOMARKER RESEARCH, 2023, 11 (01)
[42] Post-translational modification of RNA m6A demethylase ALKBH5 regulates ROS-induced DNA damage response
Yu, Fang
Wei, Jiangbo
Cui, Xiaolong
Yu, Chunjie
Ni, Wei
Bungert, Jorg
Wu, Lizi
He, Chuan
Qian, Zhijian
NUCLEIC ACIDS RESEARCH, 2021, 49 (10) : 5779 - 5797
[43] RBM33 is a unique m6A RNA-binding protein that regulates ALKBH5 demethylase activity and substrate selectivity
Yu, Fang
Zhu, Allen C.
Liu, Shun
Gao, Boyang
Wang, Yuzhi
Khudaverdyan, Nelli
Yu, Chunjie
Wu, Qiong
Jiang, Yunhan
Song, Jikui
Jin, Lingtao
He, Chuan
Qian, Zhijian
MOLECULAR CELL, 2023, 83 (12) : 2003 - +
[44] Hepatic ALKBH5 Regulation of Glucose and Lipid Metabolism
Aamodt, Kristie
Polay, Madison
Gonzales, Valeria R. Salerno
Kulkarni, Rohit
DIABETES, 2023, 72
[45] The functional role of m6A demethylase ALKBH5 in cardiomyocyte hypertrophy
Meng, Chen
Su, Haibi
Shu, Meiling
Shen, Feng
Lu, Yijie
Wu, Shishi
Su, Zhenghua
Yu, Mengyao
Yang, Di
CELL DEATH & DISEASE, 2024, 15 (09):
[46] RNA demethylase ALKBH5 promotes colorectal cancer progression by posttranscriptional activation of RAB5A in an m6A-YTHDF2-dependent manner
Shen, Dingcheng
Lin, Jinxin
Xie, Yumo
Zhuang, Zhuokai
Xu, Gaopo
Peng, Shaoyong
Tang, Guannan
Bai, Liangliang
Zhu, Mingxuan
Zhang, Yu
Huang, Ziying
Wang, Puning
Liu, Xiaoxia
Huang, Meijin
Luo, Yanxin
Wang, Xiaolin
Yu, Huichuan
CLINICAL AND TRANSLATIONAL MEDICINE, 2023, 13 (05):
[47] Discovery of maleimide derivatives as m6A demethylase ALKBH5 inhibitors
Liang, Luxia
Fei, Wenlong
Wang, Yingzhe
Zhang, Ze
You, Qidong
Guo, Xiaoke
BIOORGANIC & MEDICINAL CHEMISTRY, 2025, 120
[48] m6A demethylase ALKBH5 inhibits pancreatic cancer tumorigenesis by decreasing WIF-1 RNA methylation and mediating Wnt signaling
Tang, Bo
Yang, Yihua
Kang, Min
Wang, Yunshan
Wang, Yan
Bi, Yin
He, Songqing
Shimamoto, Fumio
MOLECULAR CANCER, 2020, 19 (01)
[49] Deubiquitinase USP9X stabilizes RNA m6A demethylase ALKBH5 and promotes acute myeloid leukemia cell survival
Wang, Peipei
Wang, Jing
Yao, Shuxin
Cui, Manman
Cheng, Ying
Liu, Weidong
Gao, Zhuying
Hu, Jin
Zhang, Jinfang
Zhang, Haojian
JOURNAL OF BIOLOGICAL CHEMISTRY, 2023, 299 (08)
[50] RNA demethylase ALKBH5 suppresses tumorigenesis via inhibiting proliferation and invasion and promoting CD8+ T cell infiltration in colorectal cancer
Ge, Jing
Liu, Sheng-Lu
Zheng, Jing-Xiu
Shi, Yu
Shao, Ying
Duan, Yu-Jing
Huang, Rui
Yang, Li-Jun
Yang, Tao
TRANSLATIONAL ONCOLOGY, 2023, 34

← 1 2 3 4 5 →