Transcription-replication conflict resolution by nuclear RNA interference.

ABSTRACT: Nuclear RNA interference (RNAi) is required for heterochromatin silencing, but Dicer also promotes genome stability by releasing RNA polymerase at sites of replication stress. R-loops are three-stranded DNA:RNA structures that accumulate at transcription-replication (T-R) collisions. We show that in RNase H-deficient cells, which accumulate pathological R-loops, Dcr1 processes R-loops at transcriptional start sites (TSSs) and end sites (TESs), releasing paused RNA polymerase and accounting for small RNAs (sRNAs) resembling DNA-damage-associated sense sRNAs (sdRNAs) found in cancer cells. Genetic evidence implicates nascent transcription-associated R-loops in genome instability in the absence of Dicer, with the helicase domain providing catalytic function reminiscent of related archaeal hel

SUBMITTER: Cheng T 

PROVIDER: S-EPMC12624956 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature