Roles of RNA-binding Proteins and Post-transcriptional Regulation in Driving Male Germ Cell Development in the Mouse

Abstract

Tissue development and homeostasis are dependent on highly regulated gene expression programs in which cell-specific combinations of regulatory factors determine which genes are expressed and the post-transcriptional fate of the resulting RNA transcripts. Post-transcriptional regulation of gene expression by RNA-binding proteins has critical roles in tissue development-allowing individual genes to generate multiple RNA and protein products, and the timing, location, and abundance of protein synthesis to be finely controlled. Extensive post-transcriptional regulation occurs during mammalian gametogenesis, including high levels of alternative mRNA expression, stage-specific expression of mRNA variants, broad translational repression, and stage-specific activation of mRNA translation. In this chapter, an overview of the roles of RNA-binding proteins and the importance of post-transcriptional regulation in male germ cell development in the mouse is presented.

Keywords: Alternative mRNA processing; Gametogenesis; Polyadenylation; Post-transcriptional regulation; RNA-binding proteins; Splicing; Translational control.

Fig. 6.1

Overview of male germ cell development in the mouse. (a) During embryogenesis, primordial germ cells (PGCs) migrate to the genital ridge where they receive signals (red dashed arrow) from gonadal support cells (Sertoli cells or granulosa cells in XY and XX embryos, respectively) and commit to a male or female program of development. (b) During the first postnatal stage of germ cell development, spermatogonia type A cells self renew or undergo a series of proliferative and differentiating divisions to generate chains of cells that will enter meiosis. (c) Meiosis involves a single genome duplication event followed by two successive divisions to generate haploid spermatids. (d) Spermiogenesis, the process by which round spermatids progress through 16 steps to transform into spermatozoa that are released into the lumen of the seminiferous tubule

Fig. 6.2

Gene regulation through alternative mRNA regulation. In this example, a single gene yields three identical pre-mRNAs that are alternatively processed into different mRNAs to alter the identity and abundance of the encoded protein. In panels (1) and (2), alternative splicing of exon ‘b’ yields mRNAs that encode alternative protein variants. In panels (2) and (3), alternative polyadenylation yields mRNAs that differ with respect to 3′UTR length, with the long 3′UTR variant (panel (3)) possessing regulatory elements that lead to reduced accumulation of the encoded protein