Work

R-loop homeostasis at transposable elements safeguards transcriptional silencing in replication-quiescent oocytes

Year: 2026

Type: article

Abstract: R-loops, though implicated in genome stability, have poorly defined transcriptional roles due to confounding replication processes in proliferating cells. Here, by leveraging replication-free oocytes and RTACC-seq, a tailored high-specificity R-loop mapping approach for low-input samples, we identify dynamic R-loop enrichment at both gene promoters and distal transposable elements. We find that transposable element-associated R-loops accumulate in transcriptionally active stage oocytes and resolve in fully grown oocytes, coinciding with chromatin condensation and transcriptional silencing. R-loops exert opposing, location-dependent regulatory functions, with reduced transcription rate at promoters and enhanced rates at transposable elements, raising the possibility of enhancer-like activity at a subset of hybrid-associated transposable element loci. In mice, oocyte-specific deletion of Rnaseh1, a gene that encodes an RNA:DNA hybrid-specific endonuclease, leads to persistent R-loops, chromatin decondensation, and impaired transcriptional silencing in fully grown oocytes, culminating in premature ovarian failure and female subfertility. These findings characterize the mechanistic basis of R-loops as mediators of chromatin remodeling, transcriptional regulation, and germ cell developmental competence. R-loops have poorly defined transcriptional roles. Here, the authors use high-specificity R-loop mapping to show that R-loops at transposable elements enhance transcription in growing oocytes, while RNase H1-mediated resolution in fully grown oocytes supports genome silencing and female fertility.

Source: Nature Communications

DOI: 10.1038/s41467-026-73781-y