HuB and HuD repress telomerase activity by dissociating HuR from TERC

HuB 和 HuD 通过将 HuR 与 TERC 分离来抑制端粒酶活性

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作者: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

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.

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