Targeting SKAP2-modulated cytoskeleton remodeling restores sperm motility

Our work recognized heterogeneous nuclear ribonucleoprotein R (hnRNPR) is a master regulator of m6A-dependent pre-mRNA splicing. Genetic mutation in HNRNPR leads to asthenoteratozoospermia in both humans and mice, culminating in complete sterility. Mechanistically, genetic ablation of Hnrnpr manifests widespread transcriptomic, proteomics, and m6A-modified splicing dysregulation, disrupting these genes essential for acrosome formation and flagellum development.