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

Nat Commun. 2017 Jan 27;8:14182. doi: 10.1038/ncomms14182.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / physiology*
  • Animals
  • Disease Models, Animal
  • Exons / genetics
  • Humans
  • Infertility, Male / genetics*
  • Infertility, Male / pathology
  • Male
  • Meiosis / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasm Proteins / physiology*
  • RNA, Messenger / physiology
  • RNA-Binding Proteins / genetics
  • Spermatocytes / physiology
  • Spermatogenesis / physiology*
  • Spermatogonia / pathology
  • Spermatogonia / physiology
  • Testis / cytology
  • Testis / pathology
  • Testis / physiology

Substances

  • BCAS2 protein, mouse
  • DAZL protein, mouse
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA-Binding Proteins