HuR regulates telomerase activity through TERC methylation. | Read by QxMD (original) (raw)
Journal Article
Research Support, Non-U.S. Gov't
Hao Tang, Hu Wang, Xiaolei Cheng, Xiuqin Fan, Fan Yang, Mengmeng Zhang, Yanlian Chen, Yuyang Tian, Cihang Liu, Dongxing Shao, Bin Jiang, Yali Dou, Yusheng Cong, Junyue Xing, Xiaotian Zhang, Xia Yi, Zhou Songyang, Wenbin Ma, Yong Zhao, Xian Wang, Jinbiao Ma, Myriam Gorospe, Zhenyu Ju, Wengong Wang
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.
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