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RNA transcripts regulate G-quadruplex landscapes through G-loop formation

ABSTRACT: G-quadruplexes (G4s) are epigenetic DNA structures that regulate transcription but also threaten genome stability when dysregulated. It remains unknown how G4 dynamics is organized in a cell-specific manner. Here, we report that RNA transcripts govern G4 landscapes through homology-directed invasion opposite the G4 strand, forming ‘G-loops’. G-loops are disassembled via DHX36-FANCJ-mediated G4 unwinding and subsequent nucleolytic incision by XPF-ERCC1, leading to hybrid strand renewal through DNA synthesis. G-loop disassembly requires stochiometric invading RNAs, by contrast, excess of which stabilizes G-loops against disassembly. Defects in G-loop disassembly accumulate G-loops predominantly in gene regulatory regions, leading to transcriptional dysregulation, replication stress, and DNA damage throughout the cell cycle. These findings establish nuclear RNAs as pivotal G-loop regulators, linking the transcriptome to gene regulation and genome maintenance.

ORGANISM(S): Mus musculus

PROVIDER: GSE268153 | GEO | 2025/06/20

REPOSITORIES: GEO

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RNA transcripts regulate G-quadruplex landscapes through G-loop formation (G4 and R-loop CUT&Tag)

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