biostudies-literatureGong DGuangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesNational Natural Science Foundation of ChinaKunming Institute of Zoology, Chinese Academy of Sciences952-968https://www.ebi.ac.uk/biostudies/studies/S-EPMC10147553biostudies-literatureUnknown18(4)Embryonic stem cells (ESCs) are superior to differentiated cells to maintain genome stability, but the underlying mechanisms remain largely elusive. R-loops are constantly formed during transcription and are inducers of DNA damage if not resolved. Here we report that mouse ESCs (mESCs) can efficiently prevent unscheduled R-loop formation, and a long noncoding RNA Lnc530 plays regulatory role. Lnc530 is expressed in mESCs and localizes on R-loops. Depletion of Lnc530 in mESCs causes R-loop accumulation and DNA damage, whereas forced expression of Lnc530 in differentiated cells suppresses the R-loop formation. Mechanistically, Lnc530 associates with DDX5 and TDP-43 in an inter-dependent manner on R-loops. Formation of Lnc530-DDX5-TDP-43 complex substantially increases the local protein levelStem cell reportsLong noncoding RNA Lnc530 localizes on R-loops and regulates R-loop formation and genomic stability in mouse embryonic stem cells.PMC1014755331930027Zhang WGong DGao JZheng PZhou HWang LfalseLong noncoding RNA Lnc530 localizes on R-loops and regulates R-loop formation and genomic stability in mouse embryonic stem cells.Embryonic stem cells (ESCs) are superior to differentiated cells to maintain genome stability, but the underlying mechanisms remain largely elusive. R-loops are constantly formed during transcription and are inducers of DNA damage if not resolved. Here we report that mouse ESCs (mESCs) can efficiently prevent unscheduled R-loop formation, and a long noncoding RNA Lnc530 plays regulatory role. Lnc530 is expressed in mESCs and localizes on R-loops. Depletion of Lnc530 in mESCs causes R-loop accumulation and DNA damage, whereas forced expression of Lnc530 in differentiated cells suppresses the R-loop formation. Mechanistically, Lnc530 associates with DDX5 and TDP-43 in an inter-dependent manner on R-loops. Formation of Lnc530-DDX5-TDP-43 complex substantially increases the local protein level2023-01-01T00:00:00Z2023 Apr2025-04-18T14:17:54.485Z2025-04-07T00:24:00.664ZS-EPMC101475533693128010.1016/j.stemcr.2023.02.003