Computational Multi-Omics

Genomic instability is frequently caused by nucleic acid structures termed R-loops that are formed during transcription. Despite their harmful potential, mechanisms that sense, signal, and suppress these structures remain elusive. We have showed that oscillations in RNA Pol II dynamics during transcription initiate a molecular pathway that prevents R-loops accumulation. Depletion of either SRPK2 or DDX23, as observed in adenoid cystic carcinoma, disrupts this pathway, leading to RNA-mediated genomic instability (Sridhara et al, Cell Reports, 2017).

Transcription is a source of genetic instability that can notably result from the formation of genotoxic DNA:RNA hybrids, R-loops, between the nascent RNA and its template. By combining the genetic manipulation of intron content with genome-wide analyses in both yeasts and human cells, we revealed a function for introns in counteracting DNA:RNA hybrid (R-loop) formation and its deleterious impact on genetic stability (Bonnet et al, Mol Cell, 2017).