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YTHDF2 Binds to 5-Methylcytosine in RNA and Modulates the Maturation of Ribosomal RNA

文献类型：期刊论文

作者Dai, Xiaoxia7,8; Gonzalez, Gwendolyn9; Li, Lin7; Li, Jie1,3,4,5; You, Changjun7,8; Miao, Weili7; Hu, Junchi6; Fu, Lijuan9; Zhao, Yonghui2; Li, Ruidong10
刊名ANALYTICAL CHEMISTRY
出版日期2020-01-07
卷号92期号:1页码:1346-1354
ISSN号0003-2700
DOI10.1021/acs.analchem.9b04505
通讯作者Gu, Weifeng(weifeng.gu@ucr.edu) ; Wang, Yinsheng(yinsheng.wang@ucr.edu)
英文摘要5-Methylcytosine is found in both DNA and RNA; although its functions in DNA are well established, the exact role of 5-methylcytidine (m(5)C) in RNA remains poorly defined. Here we identified, by employing a quantitative proteomics method, multiple candidate recognition proteins of m(5)C in RNA, including several YTH domain-containing family (YTHDF) proteins. We showed that YTHDF2 could bind directly to m(5)C in RNA, albeit at a lower affinity than that toward N-6-methyladenosine (m(6)A) in RNA, and this binding involves Trp(432), a conserved residue located in the hydrophobic pocket of YTHDF2 that is also required for m(6)A recognition. RNA bisulfite sequencing results revealed that, after CRISPR-Cas9-mediated knockout of the YTHDF2 gene, the majority of m(5)C sites in rRNA (rRNA) exhibited substantially augmented levels of methylation. Moreover, we found that YTHDF2 is involved in pre-rRNA processing in cells. Together, our data expanded the functions of the YTHDF2 protein in post-transcriptional regulations of RNA and provided novel insights into the functions of m(5)C in RNA biology.
WOS关键词STRUCTURAL BASIS ; MAPPING REVEALS ; NUCLEAR-RNA ; M(6)A RNA ; METHYLATION ; DOMAIN ; METHYLTRANSFERASE ; IDENTIFICATION ; RECOGNITION ; WIDESPREAD
资助项目National Institutes of Health[R01 ES25121] ; NRSA institutional training grant[T32 ES018827] ; National Natural Science Foundation of China[21907028]
WOS研究方向Chemistry
语种英语
WOS记录号WOS:000506719400136
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/282383]  
专题新药研究国家重点实验室
通讯作者Gu, Weifeng; Wang, Yinsheng
作者单位1.Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China
2.Univ Calif Riverside, Inst Integrat Genome Biol, Dept Bot & Plant Sci, Riverside, CA 92521 USA
3.Fudan Univ, Shanghai Canc Ctr, Dept Oncol, Shanghai 200032, Peoples R China
4.Fudan Univ, Shanghai Med Coll, Inst Biomed Sci, Shanghai 200032, Peoples R China
5.Fudan Univ, Shanghai Med Coll, Sch Basic Med Sci, Shanghai 200032, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China
7.Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA
8.Hunan Univ, Coll Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Hunan, Peoples R China
9.Univ Calif Riverside, Environm Toxicol Grad Program, Riverside, CA 92521 USA
10.Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA
推荐引用方式
GB/T 7714		 Dai, Xiaoxia,Gonzalez, Gwendolyn,Li, Lin,et al. YTHDF2 Binds to 5-Methylcytosine in RNA and Modulates the Maturation of Ribosomal RNA[J]. ANALYTICAL CHEMISTRY,2020,92(1):1346-1354.
APA Dai, Xiaoxia.,Gonzalez, Gwendolyn.,Li, Lin.,Li, Jie.,You, Changjun.,...&Wang, Yinsheng.(2020).YTHDF2 Binds to 5-Methylcytosine in RNA and Modulates the Maturation of Ribosomal RNA.ANALYTICAL CHEMISTRY,92(1),1346-1354.
MLA Dai, Xiaoxia,et al."YTHDF2 Binds to 5-Methylcytosine in RNA and Modulates the Maturation of Ribosomal RNA".ANALYTICAL CHEMISTRY 92.1(2020):1346-1354.

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来源：上海药物研究所

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