Reference: Mérida-Cerro JA, et al. (2025) Cellular imbalance of specific RNA-binding proteins associates with harmful R-loops. PLoS Genet 21(7):e1011491

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Abstract


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.

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Journal Article
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Mérida-Cerro JA, Chevreux G, Palancade B, Rondón AG, Aguilera A
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