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mRNA alternative splicing dysregulation in oocytes causes premature ovarian failure

A study · Journal of genetics and genomics = Yi chuan xue bao · Oct 24, 2026

What this means

Primordial follicle survival determines female reproductive lifespan, yet the post-transcriptional mechanisms governing this process remain incompletely understood. Here, we show that the splicing regulator SRSF2 is required for maintaining the ovarian follicle reserve through the regulation of RNA processing in oocytes.

A plain-English summary is on its way. Until then, this is the start of the authors' own summary.

Tested inNot stated
Who it was tested in
Not stated
Kind of research
A study

The science

Original title
mRNA alternative splicing dysregulation in oocytes causes premature ovarian failure.
Authors
Yue W, Li YX, Gao D et al.
Journal
Journal of genetics and genomics = Yi chuan xue bao
Published
Oct 24, 2026
Study type
Study

Abstract

Primordial follicle survival determines female reproductive lifespan, yet the post-transcriptional mechanisms governing this process remain incompletely understood. Here, we show that the splicing regulator SRSF2 is required for maintaining the ovarian follicle reserve through the regulation of RNA processing in oocytes. Oocyte-specific ablation of Srsf2 using Gdf9-Cre causes complete female infertility, progressive follicular depletion, and increased follicular apoptosis. Linear amplification of complementary DNA ends and sequencing (LACE-seq) identifies 1609 SRSF2-bound transcripts enriched in RNA-regulatory and cellular homeostasis-related processes. Subsequent RNA-seq analysis reveals broad transcriptomic and alternative-splicing dysregulation after Srsf2 loss, including prominent exon 7 skipping of the oocyte-specific transcription factor Nobox and a marked reduction in full-length NOBOX protein. Supplementation with correctly spliced Nobox mRNA partially rescues follicular developmental defects in vitro, supporting Nobox as a functionally important downstream target rather than the sole mediator of the Srsf2-deficient phenotype. Together, these findings identify SRSF2-dependent RNA processing as an important regulator of oocyte and follicle homeostasis and suggest that disruption of SRSF2-regulated splicing may contribute to ovarian insufficiency.

Read it on PubMed ↗

Yue W, Li YX, Gao D et al. mRNA alternative splicing dysregulation in oocytes causes premature ovarian failure. Journal of genetics and genomics = Yi chuan xue bao. 2026. doi:10.1016/j.jgg.2026.10.011. PMID: 42925916. https://pubmed.ncbi.nlm.nih.gov/42925916/

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