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DOI | 10.1038/s41467-019-08971-y |
HuR regulates telomerase activity through TERC methylation | |
Tang, Hao1,2; Wang, Hu3,4; Cheng, Xiaolei1; Fan, Xiuqin1; Yang, Fan3,5; Zhang, Mengmeng6; Chen, Yanlian7; Tian, Yuyang7; Liu, Cihang1; Shao, Dongxing1; Jiang, Bin1; Dou, Yali8; Cong, Yusheng3,4; Xing, Junyue1; Zhang, Xiaotian1; Yi, Xia1; Zhou Songyang7; Ma, Wenbin7; Zhao, Yong7; Wang, Xian2; Ma, Jinbiao6; Gorospe, Myriam9; Ju, Zhenyu3,4; Wang, Wengong1 | |
2019-03-04 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | Peoples R China; Germany; USA |
英文摘要 | Telomerase consists of the catalytic protein TERT and the RNA TERC. Mutations in TERC are linked to human diseases, but the underlying mechanisms are poorly understood. Here we report that the RNA-binding protein HuR associates with TERC and promotes the assembly of the TERC/TERT complex by facilitating TERC C106 methylation. Dyskeratosis congenita (DC)-related TERC U100A mutation impair the association of HuR with TERC, thereby reducing C106 methylation. Two other TERC mutations linked to aplastic anemia and autosomal dominant DC, G107U, and GC107/108AG, likewise disrupt methylation at C106. Loss-of-HuR binding and hence lower TERC methylation leads to decreased telomerase activity and telomere shortening. Furthermore, HuR deficiency or mutation of mTERC HuR binding or methylation sites impair the renewal of mouse hematopoietic stem cells, recapitulating the bone marrow failure seen in DC. Collectively, our findings reveal a novel function of HuR, linking HuR to telomerase function and TERC-associated DC. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000434379800010 |
WOS关键词 | RNA ; IDENTIFICATION ; PURIFICATION ; DYSFUNCTION ; INTERACTS ; COMPONENT ; CELLS ; TPP1 ; POT1 |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204244 |
专题 | 资源环境科学 |
作者单位 | 1.Peking Univ, Beijing Key Lab Prot Posttranslat Modificat & Cel, Dept Biochem & Mol Biol, Sch Basic Med Sci,Hlth Sci Ctr, 38 Xueyuan Rd, Beijing 100191, Peoples R China; 2.Peking Univ, Dept Physiol & Pathophysiol, Sch Basic Med Sci, Hlth Sci Ctr, 38 Xueyuan Rd, Beijing 100191, Peoples R China; 3.Jinan Univ, Inst Aging & Regenerat Med, Key Lab Regenerat Med, Minist Educ, Guangzhou 510632, Guangdong, Peoples R China; 4.Hangzhou Normal Univ, Inst Aging Res, Sch Med, Hangzhou 311121, Zhejiang, Peoples R China; 5.Friedrich Schiller Univ Jena, Fritz Lipmann Inst, Leibniz Inst Age Res, D-07745 Jena, Germany; 6.Fudan Univ, Sch Life Sci, Dept Biochem, 2005 Rd Songhu, Shanghai 200433, Peoples R China; 7.Sun Yat Sen Univ, Key Lab Gene Engn, Minist Educ, State Key Lab Biocontrol,Sch Life Sci, Guangzhou 510006, Guangdong, Peoples R China; 8.Univ Michigan, Dept Pathol & Biol Chem, 1301 Catherine St, Ann Arbor, MI 48105 USA; 9.NIA, Lab Genet & Genom, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA |
推荐引用方式 GB/T 7714 | Tang, Hao,Wang, Hu,Cheng, Xiaolei,et al. HuR regulates telomerase activity through TERC methylation[J]. NATURE COMMUNICATIONS,2019,9. |
APA | Tang, Hao.,Wang, Hu.,Cheng, Xiaolei.,Fan, Xiuqin.,Yang, Fan.,...&Wang, Wengong.(2019).HuR regulates telomerase activity through TERC methylation.NATURE COMMUNICATIONS,9. |
MLA | Tang, Hao,et al."HuR regulates telomerase activity through TERC methylation".NATURE COMMUNICATIONS 9(2019). |
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