在DNA双链断裂时,Drosha,Dicer和损伤诱导的长ncRNA控制BMI1依赖的转录抑制
Francesca Esposito1, Ilaria Capozzo2, Adelaide Riccardi2
1Istituto di Genetica Molecolare, CNR - Consiglio Nazionale delle Ricerche, 27100 Pavia, Italy; PhD Program in Genetics, Molecular and Cellular Biology (GMCB), University of Pavia, 27100 Pavia, Italy.
Cell reports
|December 5, 2025
概括
DNA损伤反应 (DDR) 通过在cis (DISC) 中的DSB诱导的沉默来沉默附近的基因. 这项研究表明,损伤诱导的长非编码RNAs (dilncRNAs),DROSHA和DICER通过促进PRC1招募来调节DISC.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 细胞生物学 细胞生物学
背景情况:
- DNA损伤反应 (DDR) 对于保持基因组稳定性至关重要.
- DNA双链断裂 (DSBs) 引发复杂的细胞反应,包括在断裂部位附近的转录沉默 (cis,DISC中的DSB诱导沉默).
- DISC涉及ATM激酶和BMI1,一个多抑制综合体1 (PRC1) 组件,同时还产生损伤诱导的长非编码RNA (dilncRNAs).
研究的目的:
- 阐明 dilncRNAs,DROSHA 和 DICER 在调节 DISC. 的作用.
- 研究这些因素影响DISC和PRC1招聘的分子机制.
主要方法:
- 抑制MRN或ATM激酶的发生.
- 使用enoxacin激活DICER的激活.
- 使用反感性寡核酸和Cas13.3阻断dilncRNAs.
- 在DSB评估BMI1招募和H2A-K119无处不在.
主要成果:
- DISC因MRN或ATM抑制而被破坏,但通过DICER激活而恢复.
- 德罗莎和迪塞尔在DSB中促进了BMI1的招募和H2A-K119的无处不在.
- BMI1以DICER-依赖的方式与DROSHA和dilncRNAs相互作用.
- 阻断dilncRNAs会损害BMI1的招募和DISC.
结论:
- DROSHA,DICER和dilncRNAs是DISC的关键调节者.
- 这些因素通过促进PRC1的招募和随后的DSBs的染色质修饰来调解DISC.
- 这一途径突出了在DDR中将RNA处理和染色体调节联系在一起的新机制.
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