HuB and HuD repress telomerase activity by dissociating HuR from TERC

Xiaolei Cheng; Xiaoping Gu; Tianjiao Xia; Zhengliang Ma; Zhongzhou Yang; Helen Lechen Feng; Yong Zhao; Wenbin Ma; Zhenyu Ju; Myriam Gorospe; Xia Yi; Hao Tang; Wengong Wang

doi:10.1093/nar/gkab062

HuB and HuD repress telomerase activity by dissociating HuR from TERC

Nucleic Acids Res. 2021 Mar 18;49(5):2848-2858. doi: 10.1093/nar/gkab062.

Authors

Xiaolei Cheng^{1

2}, Xiaoping Gu³, Tianjiao Xia³, Zhengliang Ma³, Zhongzhou Yang⁴, Helen Lechen Feng⁵, Yong Zhao⁶, Wenbin Ma⁶, Zhenyu Ju⁷, Myriam Gorospe⁸, Xia Yi¹, Hao Tang², Wengong Wang^{1

9}

Affiliations

¹ Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China.
² National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine, Heart Center of Henan Provincial People's Hospital, Central China Fuwai Hospital of Zhengzhou University, Central China Fuwai Hospital & Central China Branch of National Center for Cardiovascular Diseases, Zhengzhou, Henan 450003, China.
³ Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical Department, Nanjing University, Nanjing 210000, China.
⁴ State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.
⁵ Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USA.
⁶ Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, China.
⁷ Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou 510632, China.
⁸ Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, 251 Bayview Blvd., Baltimore, MD 21224, USA.
⁹ Center for Healthy Aging, Changzhi Medical College, Changzhi 046000, China.

Abstract

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.

Publication types

Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cellular Senescence
ELAV-Like Protein 1 / antagonists & inhibitors
ELAV-Like Protein 1 / metabolism*
ELAV-Like Protein 2 / metabolism*
ELAV-Like Protein 4 / metabolism*
Humans
RNA / metabolism*
Telomerase / metabolism*

Substances

ELAV-Like Protein 1
ELAV-Like Protein 2
ELAV-Like Protein 4
ELAVL1 protein, human
ELAVL2 protein, human
ELAVL4 protein, human
telomerase RNA
RNA
TERT protein, human
Telomerase