The post-transcriptional RNA splicing landscape driving oocyte division

Abstract

During growth in ovaries, mammalian oocytes accumulate maternal transcripts, proteins, and metabolites that support meiotic divisions and embryogenesis. As oocytes become fully grown, RNA Polymerase II is degraded and transcription is effectively silenced. However, RNA splicing appears to be required for oocyte division, a requirement which remains poorly characterized. Here, we define this post-transcriptional RNA splicing landscape of fully grown mouse oocytes and develop a computational resource that identifies post-transcriptional splicing events, signatures, sequence features, and protein binding motifs responsive to splicing perturbation. We show that, unlike transcription, RNA splicing in fully grown oocytes is essential for meiotic progression. Applying our resource across perturbations, we identify hundreds of genes whose proper splicing is required for oocyte division and reveal that distinct perturbations converge on overlapping regulatory programs controlling cytoskeletal organization and cell cycle progression that drive oocyte division. We experimentally validate selected resource-derived predictions using chemical and protein-based splicing perturbations. These findings demonstrate that extensive RNA processing persists after transcription has ceased and position post-transcriptional splicing as a fundamental regulator of mammalian oocyte development.