DNA damage: RNA-binding proteins protect from near and far

•Various RNA-binding proteins (RBPs) prevent genome instability by preventing the formation of RNA/DNA hybrids.•Several RBPs are involved in DNA repair.•Specific RBPs mediate selective regulation of DNA damage response (DDR) gene expression upon DNA damage.•RBP relocalization upon DNA damage may coordinately regulate RNA and DNA metabolism.

Recent work, including large-scale genetic and molecular analyses, identified RNA-binding proteins (RBPs) as major players in the prevention of genome instability. These studies show that RBPs prevent harmful RNA/DNA hybrids and are involved in the DNA damage response (DDR), from DNA repair to cell survival decisions. Indeed, specific RBPs allow the selective regulation of DDR genes at multiple post-transcriptional levels (from pre-mRNA splicing/polyadenylation to mRNA stability/translation) and are directly involved in DNA repair. These multiple activities are mediated by RBP binding to mRNAs, nascent transcripts, noncoding RNAs, and damaged DNA. Finally, because DNA damage modifies RBP localization and binding to different RNA/DNA molecules, we propose that upon DNA damage, RBPs coordinately regulate various aspects of both RNA and DNA metabolism.