RNA-binding proteins in spermatogenesis: functional mechanisms, clinical potential, and future perspectives

RNA-binding proteins (RBPs) govern RNA splicing, stability, translation, and localization through RNA-recognition motifs, K-homology domains, and related structures, orchestrating spermatogonial stem cell (SSC) self-renewal, meiosis, and spermiogenesis. We present the stage-specific roles of key RBPs, such as deleted in azoospermia protein/deleted in azoospermia-like protein (DAZ/DAZL), nanos C2HC-type zinc finger 2 (NANOS2), P-element-induced wimpy testis protein (PIWI) family members, and tudor domain-containing 6 (TDRD6), and illustrate their molecular mechanisms in SSC maintenance, meiotic progression, and sperm morphogenesis. The review assesses RBP expression and modifications as diagnostic biomarkers for male infertility, evaluates RBP-targeted therapies, and notes translational obstacles. Emerging interdisciplinary approaches promise to decode spatiotemporal RBP networks and advance precision diagnosis and treatment of male reproductive disorders.