Linking circular intronic RNA degradation and function in transcription by RNase H1

Abstract

Circular intronic RNAs (ciRNAs) escaping from DBR1 debranching of intron lariats are co-transcriptionally produced from pre-mRNA splicing, but their turnover and mechanism of action have remained elusive. We report that RNase H1 degrades a subgroup of ciRNAs in human cells. Many ciRNAs contain high GC% and tend to form DNA:RNA hybrids (R-loops) for RNase H1 cleavage, a process that appears to promote Pol II transcriptional elongation at ciRNA-producing loci. One ciRNA, ciankrd52, shows a stronger ability of R-loop formation than that of its cognate pre-mRNA by maintaining a locally open RNA structure in vitro. This allows the release of pre-mRNA from R-loops by ci-ankrd52 replacement and subsequent ciRNA removal via RNase H1 for efficient transcriptional elongation. We propose that such an R-loop dependent ciRNA degradation likely represents a mechanism that on one hand limits ciRNA accumulation by recruiting RNase H1 and on the other hand resolves R-loops for transcriptional elongation at some GC-rich ciRNA-producing loci.

Keywords: DNA:RNA hybrid; R-loop; RNase H1; ci-ankrd52; ciRNA; ciRNA structure; circular intronic RNA; transcriptional elongation.