BCAS2 is involved in alternative mRNA splicing in spermatogonia and the transition to meiosis

Abstract

Breast cancer amplified sequence 2 (BCAS2) is involved in multiple biological processes, including pre-mRNA splicing. However, the physiological roles of BCAS2 are still largely unclear. Here we report that BCAS2 is specifically enriched in spermatogonia of mouse testes. Conditional disruption of Bcas2 in male germ cells impairs spermatogenesis and leads to male mouse infertility. Although the spermatogonia appear grossly normal, spermatocytes in meiosis prophase I and meiosis events (recombination and synapsis) are rarely observed in the BCAS2-depleted testis. In BCAS2 null testis, 245 genes are altered in alternative splicing forms; at least three spermatogenesis-related genes (Dazl, Ehmt2 and Hmga1) can be verified. In addition, disruption of Bcas2 results in a significant decrease of the full-length form and an increase of the short form (lacking exon 8) of DAZL protein. Altogether, our results suggest that BCAS2 regulates alternative splicing in spermatogonia and the transition to meiosis initiation, and male fertility.

Mettl3-mediated m6A regulates spermatogonial differentiation and meiosis initiation

“…Our findings demonstrated an additional mechanism for METTL3 in spermatogenesis by regulating the alternative splicing of mRNAs. We found that many important spermatogenesis-regulating genes, such as Sohlh1 and Dazl [35][36][37]49], carried m 6 A modification and exhibited altered splicing pattern in Mettl3 cKO mice. This indicates that the loss of m 6 A modification on these genes upon Mettl3 deletion indeed influenced their alternative splicing pattern and resulted in defective spermatogenesis.…”

“…DNA methylation and demethylation, histone modification, together with lncRNAs, microRNAs, piR-NA and many transcriptional factors have been shown to participate in regulating spermatogenic progression by modulating gene expression [42][43][44][45][46][47][48]. Alternative splicing is another important mechanism to regulate gene expression, and a recent report showed that Bcas2, an important alternative splicing factor, functions in spermatogonia and is involved in the transition to meiosis through regulating alternative mRNA splicing [49].…”

DNA oxidation induced by fetal exposure to BPA agonists impairs female meiosis

“…The exact role of this program is unclear but is though to be required for stabilization of meiotic transcripts during prophase I of meiosis (Liu et al, 2017;. As observed in adult testis, modulation of this program results in spermatogenesis defects, highlighting the essential role of the RNA splicing during meiosis (Hannigan et al, 2017;Liu et al, 2017). For this reason, we studied the impact of bisphenols exposure on RNA splicing events during meiosis initiation.…”

“…A regulated alternative splicing program has been reported during meiosis initiation in male and in female germ cells (Naro et al, 2017;. The exact role of this program is unclear but is though to be required for stabilization of meiotic transcripts during prophase I of meiosis (Liu et al, 2017;. As observed in adult testis, modulation of this program results in spermatogenesis defects, highlighting the essential role of the RNA splicing during meiosis (Hannigan et al, 2017;Liu et al, 2017).…”

“…Moreover, bisphenol exposure also induced a global alteration of splicing events during this step. Recent studies have highlighted the role of mRNA splicing on the mitosis to meiosis transition in male and female germ cells and lack of splicing regulators in male germ cells leads to meiotic defects (Liu et al, 2017;Naro et al, 2017;Schmid et al, 2013;. In consequences, minor modifications of the splicing of meiotic genes after bisphenols exposure could impact meiosis.…”