N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation

被引：315

作者：

Ma, Honghui ^{[1
,2
,3
,4
,5
]}

Wang, Xiaoyun ^{[6
]}

Cai, Jiabin ^{[7
]}

Dai, Qing ^{[3
,4
,5
]}

Natchiar, S. Kundhavai ^{[8
]}

Lv, Ruitu ^{[1
,2
]}

Chen, Kai ^{[3
,4
,5
]}

Lu, Zhike ^{[3
,4
,5
]}

Chen, Hao ^{[1
,2
]}

Shi, Yujiang Geno ^{[1
,2
,9
]}

Lan, Fei ^{[1
,2
]}

Fan, Jia ^{[7
]}

Klaholz, Bruno P. ^{[8
]}

Pan, Tao ^{[6
]}

Shi, Yang ^{[1
,2
,10
]}

He, Chuan ^{[3
,4
,5
,6
]}

机构：

[1] Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Shanghai, Peoples R China

[2] Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China

[3] Univ Chicago, Dept Chem, 5735 S Ellis Ave, Chicago, IL 60637 USA

[4] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA

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

[6] Univ Chicago, Dept Biochem & Mol Biol, 920 E 58th St, Chicago, IL 60637 USA

[7] Fudan Univ, Key Lab Carcinogenesis & Canc Invas, Minist Educ, Zhongshan Hosp,Liver Canc Inst, Shanghai, Peoples R China

[8] Univ Strasbourg, Ctr Integrat Biol CBI, Dept Integrated Struct Biol, Inst Genet & Mol & Cellular Biol IGBMC,CNRS,Inser, Illkirch Graffenstaden, France

[9] Harvard Med Sch, Brigham & Womens Hosp, Endocrinol Div, Boston, MA USA

[10] Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA

来源：

NATURE CHEMICAL BIOLOGY | 2019年 / 15卷 / 01期

基金：

中国国家自然科学基金; 美国国家卫生研究院;

关键词：

MESSENGER-RNA; GENE-EXPRESSION; NUCLEAR-RNA; M(6)A METHYLTRANSFERASE; SUBUNIT; N6-METHYLADENOSINE; STABILITY; PROTEINS; INSIGHTS; METTL16;

D O I：

10.1038/s41589-018-0184-3

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) RNA modification is present in messenger RNAs (mRNA), ribosomal RNAs (rRNA), and spliceosomal RNAs (snRNA) in humans. Although mRNA m(6)A modifications have been extensively studied and shown to play critical roles in many cellular processes, the identity of m(6)A methyltransferases for rRNAs and the function of rRNA m(6)A modifications are unknown. Here we report a new m(6)A methyltransferase, ZCCHC4, which primarily methylates human 28S rRNA and also interacts with a subset of mRNAs. ZCCHC4 knockout eliminates m 6 A4220 modification in 28S rRNA, reduces global translation, and inhibits cell proliferation. We also find that ZCCHC4 protein is overexpressed in hepatocellular carcinoma tumors, and ZCCHC4 knockout significantly reduces tumor size in a xenograft mouse model. Our results highlight the functional significance of an rRNA m(6)A modification in translation and in tumor biology.

引用

页码：88 / +

页数：11

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