HuB 和 HuD 通过使 HuR 与 TERC 分离来抑制端粒酶活性。
HuB and HuD repress telomerase activity by dissociating HuR from TERC.
机构信息
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.
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.
出版信息
Nucleic Acids Res. 2021 Mar 18;49(5):2848-2858. doi: 10.1093/nar/gkab062.
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.
普遍存在的 RNA 结合蛋白 HuR（ELAVL1）通过与端粒酶非编码 RNA TERC 结合来促进端粒酶活性。然而，神经特异性成员 HuB、HuC 和 HuD（ELAVL2-4）在端粒酶活性中的作用尚不清楚。在这里，我们报告 HuB 和 HuD，但不是 HuC，抑制人神经母细胞瘤细胞中端粒酶的活性。HuB 和 HuD 通过与 TERC 中的富含 AU 序列结合，抑制 TERT-TERC 核心复合物的组装。此外，HuB 和 HuD 与 HuR 竞争结合 TERC，并拮抗 HuR 的功能，先前的研究表明 HuR 增强端粒酶活性以促进细胞生长。我们的发现揭示了一种新的机制，该机制控制人神经母细胞瘤细胞中端粒酶的活性，涉及 HuR 与相关的神经特异性蛋白 HuB 和 HuD 之间的竞争。
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