R-loop and its functions at the regulatory interfaces between transcription and (epi)genome

Abstract

R-loop represents a prevalent and specialized chromatin structure critically involved in a wide range of biological processes. In particular, co-transcriptional R-loops, produced often due to RNA polymerase pausing or RNA biogenesis malfunction, can initiate molecular events to context-dependently regulate local gene transcription and crosstalk with chromatin modifications. Cellular "readers" of R-loops are identified, exerting crucial impacts on R-loop homeostasis and gene regulation. Mounting evidence also supports R-loop deregulation as a frequent, sometimes initiating, event during the development of human pathologies, notably cancer and neurological disorder. The purpose of this review is to cover recent advances in understanding the fundamentals of R-loop biology, which have started to unveil complex interplays of R-loops with factors involved in various biological processes such as transcription, RNA processing and epitranscriptomic modification (such as N6-methyladenosine), DNA damage sensing and repair, and epigenetic regulation.

Keywords: Cancer; Chromatin; DNA; DNA damage; N(6)-methyladenosine; R loop; RNA; RNA-DNA hybrid; Splicing; Transcription.