HuB and HuD repress telomerase activity by dissociating HuR from TERC

被引:11
作者
Cheng, Xiaolei [1 ,2 ,3 ]
Gu, Xiaoping [4 ]
Xia, Tianjiao [4 ]
Ma, Zhengliang [4 ]
Yang, Zhongzhou [5 ,6 ]
Feng, Helen Lechen [7 ]
Zhao, Yong [8 ]
Ma, Wenbin [8 ]
Ju, Zhenyu [9 ]
Gorospe, Myriam [10 ]
Yi, Xia [1 ]
Tang, Hao [2 ,3 ]
Wang, Wengong [1 ,11 ]
机构
[1] Peking Univ Hlth Sci Ctr, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing Key Lab Prot Posttranslat Modificat & Cel, 38 Xueyuan Rd, Beijing 100191, Peoples R China
[2] Zhengzhou Univ, Cent China Fuwai Hosp, Henan Prov Peoples Hosp, Heart Ctr,Key Lab Cardiovasc Regenerat Med,Natl H, Zhengzhou 450003, Henan, Peoples R China
[3] Natl Ctr Cardiovasc Dis, Cent China Branch, Zhengzhou 450003, Henan, Peoples R China
[4] Nanjing Univ, Dept Anesthesiol, Affiliated Drum Tower Hosp, Med Dept, Nanjing 210000, Peoples R China
[5] Nanjing Univ, Model Anim Res Ctr, Nanjing Biomed Res Inst, State Key Lab Pharmaceut Biotechnol, Nanjing 210061, Peoples R China
[6] Nanjing Univ, Model Anim Res Ctr, Nanjing Biomed Res Inst, MOE Key Lab Model Anim Dis Study, Nanjing 210061, Peoples R China
[7] Boston Univ, Dept Biol, 5 Cummington Mall, Boston, MA 02215 USA
[8] Sun Yat Sen Univ, Sch Life Sci, Key Lab Gene Engn, State Key Lab Biocontrol,Minist Educ, Guangzhou 510006, Peoples R China
[9] Jinan Univ, Inst Aging & Regenerat Med, Key Lab Regenerat Med, Minist Educ, Guangzhou 510632, Peoples R China
[10] NIA, Lab Genet & Genom, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA
[11] Changzhi Med Coll, Ctr Hlth Aging, Changzhi 046000, Peoples R China
关键词
RNA-BINDING PROTEINS; ELAV; INTERACTS; TPP1; POT1;
D O I
10.1093/nar/gkab062
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
The ubiquitous RNA-binding protein HuR (ELAVL1) promotes telomerase activity by associating with the telomerase noncoding RNA TERC. However, the role of the neural-specific members HuB, HuC, and HuD (ELAVL2-4) in telomerase activity is unknown. Here, we report that HuB and HuD, but not HuC, repress telomerase activity in human neuroblastoma cells. By associating with AU-rich sequences in TERC, HuB and HuD repressed the assembly of the TERT-TERC core complex. Furthermore, HuB and HuD competed with HuR for binding to TERC and antagonized the function of HuR that was previously shown to enhance telomerase activity to promote cell growth. Our findings reveal a novel mechanism controlling telomerase activity in human neuroblastoma cells that involves a competition between HuR and the related, neural-specific proteins HuB and HuD.
引用
收藏
页码:2848 / 2858
页数:11
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