ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility.
ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility.
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DOI：
10.1016/j.molcel.2012.10.015
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发表时间：
2013-01-10
期刊：
影响因子：
16
通讯作者：
He, Chuan
中科院分区：
文献类型：
--
作者：
Zheng, Guanqun;Dahl, John Arne;Niu, Yamei;Fedorcsak, Peter;Huang, Chun-Min;Li, Charles J.;Vagbo, Cathrine B.;Shi, Yue;Wang, Wen-Ling;Song, Shu-Hui;Lu, Zhike;Bosmans, Ralph P. G.;Dai, Qing;Hao, Ya-Juan;Yang, Xin;Zhao, Wen-Ming;Tong, Wei-Min;Wang, Xiu-Jie;Bogdan, Florian;Furu, Kari;Fu, Ye;Jia, Guifang;Zhao, Xu;Liu, Jun;Krokan, Hans E.;Klungland, Arne;Yang, Yun-Gui;He, Chuan
n6 -甲基腺苷（m6A）是高等真核生物中最常见的信使RNA （mRNA）内部修饰。在这里，我们报道了ALKBH5作为另一种哺乳动物去甲基化酶，在体外和体内氧化逆转mRNA中的m6A。ALKBH5的这种去甲基化活性显著影响核斑中mRNA的输出和RNA的代谢以及mRNA加工因子的组装。alkbh5缺陷雄性小鼠mRNA中m6A含量增加，其特征是减数分裂中期精细胞凋亡导致生育能力受损。根据这一缺陷，我们在小鼠睾丸中发现了1551个差异表达基因，涵盖了广泛的功能类别，包括参与p53功能相互作用网络的精子发生相关mrna。这种RNA去甲基化酶的发现强烈表明，可逆的m6A修饰在哺乳动物细胞中具有基本和广泛的功能。
N6-methyladenosine (m6A) is the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Here we report ALKBH5 as another mammalian demethylase that oxidatively reverses m6A 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 m6A 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 m6A modification has fundamental and broad functions in mammalian cells.
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DOI：
10.1023/a:1009752804126
发表时间：
1998-01-01
期刊：
Methods in Cell Science
影响因子：
--
作者：
Haukenes, Gunnar;Kalland, Karl-Henning
通讯作者：
Kalland, Karl-Henning
影响因子：
4.7
作者：
He, Chunjiang;Zuo, Zhixiang;Zhou, Rongjia
通讯作者：
Zhou, Rongjia
影响因子：
5.3
作者：
CAMPER, SA;ALBERS, RJ;ROTTMAN, FM
通讯作者：
ROTTMAN, FM
影响因子：
16
作者：
Gilbert, W;Guthrie, C
通讯作者：
Guthrie, C
影响因子：
14.9
作者：
Bodi Z;Button JD;Grierson D;Fray RG
通讯作者：
Fray RG