Reynolds Nicola, Collier Brian, Maratou Klio, Bingham Victoria, Speed Robert M, Taggart Mary, Semple Colin A, Gray Nicola K, Cooke Howard J
MRC Human Genetics Unit, Western General Hospital, University of Edinburgh, UK.
Hum Mol Genet. 2005 Dec 15;14(24):3899-909. doi: 10.1093/hmg/ddi414. Epub 2005 Nov 8.
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.
配子发生是一个复杂的过程,在转录和翻译水平上都受到严格控制。DAZ基因编码的一个保守的RNA结合蛋白家族成员对于该过程所必需的基因表达的翻译调控是必需的。尽管DAZ家族基因的缺失与包括人类在内的多种生物的不育有关,但体内受调控的转录本的身份尚不清楚。通过结合免疫沉淀和微阵列分析,我们已经鉴定出一些在体内和体外都与小鼠Dazl蛋白结合的mRNA。序列分析表明,这些转录本包含Dazl的结合位点,这些位点在人类、大鼠和小鼠之间的进化过程中是保守的。我们重点研究了小鼠vasa同源物(Mvh),这是一个对雄性配子发生至关重要的基因,并表明Dazl通过Mvh 3'-UTR刺激翻译。最后,我们表明Dazl基因敲除小鼠的生殖细胞中Mvh蛋白水平降低,表明Dazl介导的Mvh翻译调控对哺乳动物精子发生至关重要。