Dazl binds in vivo to specific transcripts and can regulate the pre-meiotic translation of Mvh in germ cells

Abstract

Gametogenesis is a complex process subject to strict controls at both levels of transcription and translation. Members of a family of conserved RNA-binding proteins encoded by the DAZ genes are required for the translational regulation of gene expression essential for this process. Although loss of DAZ family genes is associated with infertility in several organisms including humans, the identity of the transcripts regulated in vivo is unknown. Using a combination of immunoprecipitation and microarray analysis, we have identified a number of mRNAs that are bound by the murine Dazl protein both in vivo and in vitro. Sequence analysis shows that these transcripts contain binding sites for Dazl, which have been conserved during evolution between human, rat and mouse. We have focussed on mouse vasa homologue (Mvh), a gene that is essential for male gametogenesis, and show that Dazl stimulates translation via the Mvh 3'-UTR. Finally, we show that germ cells of Dazl null mice contain reduced levels of Mvh protein, indicating that Dazl-mediated regulation of Mvh translation is crucial for mammalian spermatogenesis.

Deleted in Azoospermia-Like Enhances In Vitro Derived Porcine Germ Cell Formation and Meiosis

“…These findings confirm the previously established regulatory role of DAZL on the expression of SCP3 and VASA in our in vitro derived germ cell system. DAZL has been shown to interact with Mvh mRNA, stimulating its translation in germ cells by binding to a site within the 3¢ UTR of the Mvh transcript [28]. Germ cells derived from Dazl knockout mice contain lower levels of MVH (VASA) protein, suggesting that the RNAbinding activity of the DAZL protein mediates regulation of Mvh translation in vivo [28].…”

“…DAZL has been shown to interact with Mvh mRNA, stimulating its translation in germ cells by binding to a site within the 3¢ UTR of the Mvh transcript [28]. Germ cells derived from Dazl knockout mice contain lower levels of MVH (VASA) protein, suggesting that the RNAbinding activity of the DAZL protein mediates regulation of Mvh translation in vivo [28]. A similar regulatory mechanism was also reported to control Scp3 expression, in which DAZL facilitates Scp3 translation by interacting with the 3¢UTR of the Scp3 transcript [17].…”

GDNF Signaling Regulates YBX1/mRNA Interactions in Mouse Spermatogonia.

“…DAZL is suggested to positively regulate the translation of the mRNA it binds, including DDX4 mRNA. DDX4 is a part of chromatoid bodies where RNA can be stored; there the transcripts DDX4 binds can be regulated by its acetylation [3,6,7].…”

“…DAZ member proteins are stimulators of translation. The target mRNAs of DAZ family member DAZL, include MVH (mouse VASA homologue), another gene critical for spermatogenesis [2][3][4]157].…”

The role of spermatogonially expressed germ cell-specific genes in mammalian meiosis

“…Strikingly, a number of gene transcripts in Table 1 appear to be DAZL-binding targets (Sycp3, Tex19, Mvh, Stk31, Tex14, Tuba3, and Fthl17). Furthermore, it has also been shown that DAZL stimulates translation of Mvh by binding to its 3 ¶ untranslated region (UTR) (Reynolds et al 2005).…”