研究动态
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RNA 结合基序蛋白 14 调节 TERRA 和端粒 R 环界面处的端粒完整性。

The RNA-binding motif protein 14 regulates telomere integrity at the interface of TERRA and telomeric R-loops.

发表日期:2023 Nov 01
作者: Yajun Wang, Wei Zhu, Yumi Jang, Joshua A Sommers, Gong Yi, Chandrakala Puligilla, Deborah L Croteau, Yibin Yang, Mihoko Kai, Yie Liu
来源: NUCLEIC ACIDS RESEARCH

摘要:

含有端粒重复的 RNA (TERRA) 及其形成的 RNA:DNA 杂合体(或 TERRA R 环)会影响端粒的维持,特别是在使用同源重组介导的端粒选择性延长的人类癌细胞中。在这里,我们报告 RNA 结合基序蛋白 14 (RBM14) 与人类癌细胞中的端粒相关。 RBM14 负向调节 TERRA 表达。它还与 TERRA 结合并抑制其在端粒处形成 TERRA R 环。 RBM14 缺失会产生多种影响,包括 TERRA 水平升高、端粒 R 环、端粒功能障碍诱导的 DNA 损伤灶形成,特别是在存在 DNA 复制应激、pRPA32 在端粒和端粒无信号末端积累的情况下。因此,RBM14 通过调节 TERRA 水平及其在端粒上的 R 环形成来保护端粒完整性。© 作者 2023。由牛津大学出版社代表 Nucleic Acids Research 出版 2023。
Telomeric repeat-containing RNA (TERRA) and its formation of RNA:DNA hybrids (or TERRA R-loops), influence telomere maintenance, particularly in human cancer cells that use homologous recombination-mediated alternative lengthening of telomeres. Here, we report that the RNA-binding motif protein 14 (RBM14) is associated with telomeres in human cancer cells. RBM14 negatively regulates TERRA expression. It also binds to TERRA and inhibits it from forming TERRA R-loops at telomeres. RBM14 depletion has several effects, including elevated TERRA levels, telomeric R-loops, telomere dysfunction-induced DNA damage foci formation, particularly in the presence of DNA replication stress, pRPA32 accumulation at telomeres and telomere signal-free ends. Thus, RBM14 protects telomere integrity via modulating TERRA levels and its R-loop formation at telomeres.© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research 2023.