Posttranscriptional regulation of CDC25A by BOLL is a conserved fertility mechanism essential for human spermatogenesis.

Abstract

Human BOLL is known as a meiotic regulator, and CDC25A is considered as a potential RNA target of BOLL. The aim of the study was to clarify the relationship between BOLL and CDC25A expressions in human testes and to explore the mechanism by which BOLL regulates CDC25A. A prospective experimental study was conducted at a university-based medical center. BOLL protein, CDC25A mRNA, and CDC25A protein expressions, as well as spermatocyte numbers in the testes of 32 infertile men were measured. The interaction between BOLL protein and CDC25A mRNA was assessed in in vitro studies. Protein and RNA expressions, relationships between expression profiles, CDC25A mRNA binding site for BOLL, and the effects of BOLL on CDC25A mRNA stability and translatability were measured. The protein expressions of BOLL and CDC25A are significantly decreased in patients with spermatogenic failure, with the lowest levels detected in patients with meiotic arrest. Both protein expressions are significantly correlated with spermatocyte numbers. Expressional profiling analysis among BOLL protein, CDC25A mRNA, and CDC25A protein suggests a causal relationship between BOLL and CDC25A. BOLL specifically binds to a 21-nucleotide region of the CDC25A 3'UTR, and this region is evolutionarily conserved. A U-rich region within this 21-nucleotide sequence is crucial for binding. BOLL stimulates CDC25A translation, and this effect does not involve alteration of mRNA stability. CDC25A is subject to translational control by BOLL, which is an evolutionarily conserved mechanism. A decreased CDC25A expression caused by lack or decrease of BOLL may be associated with male infertility.