R-loop resolution promotes co-transcriptional chromatin silencing

RNA-mediated chromatin silencing is central to genome regulation in many organisms. However, how nascent non-coding transcripts regulate chromatin is poorly understood. Here, through analysis of Arabidopsis FLC, we show that resolution of a nascent-transcript-induced R-loop promotes chromatin silencing. Stabilization of an antisense-induced R-loop at the 3 end of FLC enables an RNA binding protein FCA, with its direct partner FY/WDR33 and other 3 ' -end processing factors, to polyadenylate the nascent antisense transcript. This clears the R-loop and recruits the chromatin modifiers demethylating H3K4me1. FCA immunoprecipitates with components of the m(6)A writer complex, and m(6)A modification affects dynamics of FCA nuclear condensates, and promotes FLC chromatin silencing. This mechanism also targets other loci in the Arabidopsis genome, and consistent with this fca and fy are hypersensitive to a DNA damage-inducing drug. These results show how modulation of R-loop stability by co-transcriptional RNA processing can trigger chromatin silencing. Nascent non-coding RNA can mediate chromatin silencing, however mechanistically this process is poorly understood. Here the authors show that resolution of an R-loop during 3'-end processing of a plant antisense transcript recruits chromatin modifiers to promote chromatin silencing.

Automated summary

RNA-mediated chromatin silencing plays a central role in genome regulation across various organisms. In this study, researchers demonstrated that resolution of an R-loop during 3'-end processing of a plant antisense transcript recruits chromatin modifiers to promote chromatin silencing. Additionally, modulation of R-loop stability by co-transcriptional RNA processing can trigger chromatin silencing.