Mérida-Cerro José Antonio, Chevreux Guillaume, Palancade Benoit, Rondón Ana G, Aguilera Andrés
Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Seville, Spain.
Université Paris Cité, CNRS, Institut Jacques Monod, Paris, France.
PLoS Genet. 2025 Jul 2;21(7):e1011491. doi: 10.1371/journal.pgen.1011491. eCollection 2025 Jul.
Understanding how the assembly of nascent mRNA into a ribonucleoprotein (mRNP) influences R-loop homeostasis is crucial for gaining insight into the cellular mechanisms that prevent genome instability. Here, we identify three RNA-binding proteins, Rie1, Rim4 and She2, whose expression levels are important to limit R-loop accumulation and, thus, to prevent DNA damage. Interestingly, Rim4 and She2 are overrepresented in CBP80-containing mRNPs formed in the absence of THO. In addition, we found that an excess of the RNA exosome component Dis3 impairs its function, promoting R-loops, particularly from non-coding RNAs, which cause genomic instability. Our results indicate that changes in the availability of different RBPs or RNAs, causes R-loop-mediated DNA damage in the cell. These results may help to understand the mechanism that promotes cancer, as several RBPs are overexpressed in different types of tumors.
了解新生mRNA组装成核糖核蛋白（mRNP）如何影响R环稳态，对于深入了解预防基因组不稳定的细胞机制至关重要。在这里，我们鉴定出三种RNA结合蛋白，即Rie1、Rim4和She2，它们的表达水平对于限制R环积累从而预防DNA损伤很重要。有趣的是，在缺乏THO的情况下形成的含CBP80的mRNP中，Rim4和She2的含量过高。此外，我们发现过量的RNA外切体成分Dis3会损害其功能，促进R环形成，特别是来自非编码RNA的R环，这会导致基因组不稳定。我们的结果表明，不同RNA结合蛋白或RNA可用性的变化会导致细胞中R环介导的DNA损伤。这些结果可能有助于理解促进癌症的机制，因为几种RNA结合蛋白在不同类型的肿瘤中过表达。
