Heterogeneous nuclear ribonucleoprotein L orchestrates alternative splicing critical for primordial follicle formation - PubMed
4 hours ago
- #Meiotic prophase I
- #Premature ovarian insufficiency
- #Alternative splicing
- Heterogeneous nuclear ribonucleoprotein L (hnRNPL) plays a critical role in alternative splicing (AS) during primordial follicle formation.
- Analysis of scRNA-seq and bulk RNA-seq datasets identified a peak of AS activity at E16.5-E18.5, involving 6,766 differentially spliced junctions and 3,625 genes.
- hnRNPL was identified as a key regulatory factor, and its conditional knockout (cKO) in mice led to female sterility, reduced primordial follicle formation, and premature ovarian insufficiency (POI).
- Hnrnpl cKO ovaries exhibited meiotic synapsis defects, unrepaired DNA double-strand breaks (DSBs), and thousands of aberrant AS events.
- Mechanistically, hnRNPL interacts with PTBP1 and SRSF10 to regulate splicing of genes essential for meiotic progression.
- The study suggests hnRNPL-mediated AS is vital for primordial follicle development and nominates hnRNPL as a potential POI biomarker.