核聚A结合蛋白和核利用它们的RNA识别基因来读取PAR链
Leilei Shi1, Morgan Dasovich2, John R Horton1
1Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, United States.
Nucleic acids research
|November 3, 2025
概括
研究人员发现,特定的RNA识别基因 (RRMs) 可以与RNA相似地与多ADP-ribose (PAR) 链结合. 这揭示了RRM在DNA修复和PARylation过程中的新角色.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 聚ADP-ribosyl化 (PARylation) 是一个关键的翻译后修饰,涉及PARP酶.
- PAR链作为信号分子和对接平台,用于参与DNA修复的蛋白质.
- 已知RNA识别基因 (RRMs) 能结合RNA,但它们在PAR结合中的作用不太清楚.
研究的目的:
- 系统地研究RRMs与不同长度的PAR链的相互作用.
- 确定可以结合PAR的特定RRM,并描述它们的结合性质.
- 探索RRM-PAR相互作用在DNA损伤反应中的功能影响.
主要方法:
- 对数百个重组RNA结合域进行选,以检测PAR结合的可能性.
- 对短和长PAR链的结合亲缘关系和特异性的表征.
- 在体内评估使用激光微辐射测定对DNA损伤部位的蛋白质招募.
主要成果:
- 尽管与RNA有化学相似性,但只有RRMs的一个子集被证明与PAR链结合.
- 来自多A结合蛋白 (PABPN1) 和核素 (NCL) 的RRM分别被确定为短和长 PAR 链的读取器.
- PABPN1和NCL RRMs被招募到DNA损伤部位,并表现出对PAR和RNA的竞争性结合.
结论:
- 特定的RRM具有识别和结合PAR聚合物的能力,扩大它们已知的功能表.
- 这些发现突出了PARylation和RNA结合蛋白之间的功能相互作用在细胞过程中,如DNA修复.
- 这项研究扩大了对RRM多功能性和DNA损伤反应背后的分子机制的理解.
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