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.
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Acknowledgements
We would like to thank Chen and Yang laboratories for discussion, and Qianwen Sun for providing helpful comments on DRIP assays. This work was supported by the National Natural Science Foundation of China (NSFC) (91940303, 31725009) and the HHMI International Program (55008728) to L.-L.C., NSFC (31730111, 31925011) to L.Y. and Young Elite Scientists Sponsorship Program (2020QNRC001) to X.L. L.-L. C. acknowledges the support from the XPLORER PRIZE.
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Li, X., Zhang, JL., Lei, YN. et al. Linking circular intronic RNA degradation and function in transcription by RNase H1. Sci. China Life Sci. 64, 1795–1809 (2021). https://doi.org/10.1007/s11427-021-1993-6
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DOI: https://doi.org/10.1007/s11427-021-1993-6