Smorag Lukasz, Xu Xingbo, Engel Wolfgang, Pantakani D V Krishna
Institute of Human Genetics, University of Goettingen, Goettingen, Germany.
Wiley Interdiscip Rev RNA. 2014 Jul-Aug;5(4):527-35. doi: 10.1002/wrna.1228. Epub 2014 Apr 8.
RNA-binding proteins play an important role in the regulation of gene expression by modulating translation and localization of specific messenger RNAs (mRNAs) during early development and gametogenesis. The DAZ (Deleted in Azoospermia) family of proteins, which includes DAZ, DAZL, and BOULE, are germ cell-specific RNA-binding proteins that are implicated in translational regulation of several transcripts. Of particular importance is DAZL, which is present in vertebrates and arose from the duplication of the ancestral BOULE during evolution. Identification of DAZL target mRNAs and characterization of the RNA-binding sequence through in vitro binding assays and crystallographic studies revealed that DAZL binds to GUU triplets in the 3' untranslated region of target mRNAs. Although there is compelling evidence for the role of DAZL in translation stimulation of target mRNAs, recent studies indicate that DAZL can also function in translational repression and transport of specific mRNAs. Furthermore, apart from the well-characterized function of DAZL in gametogenesis, recent data suggest its role in early embryonic development and differentiation of pluripotent stem cells toward functional gametes. In light of the mounting evidence for the role of DAZL in various cellular and developmental processes, we summarize the currently characterized biological functions of DAZL in RNA biology and development.
RNA结合蛋白在早期发育和配子发生过程中通过调节特定信使核糖核酸(mRNA)的翻译和定位,在基因表达调控中发挥重要作用。DAZ(无精子症缺失)蛋白家族,包括DAZ、DAZL和BOULE,是生殖细胞特异性RNA结合蛋白,与多种转录本的翻译调控有关。特别重要的是DAZL,它存在于脊椎动物中,是在进化过程中由祖先BOULE基因复制产生的。通过体外结合试验和晶体学研究鉴定DAZL靶mRNA并表征RNA结合序列,结果显示DAZL与靶mRNA 3'非翻译区的GUU三联体结合。尽管有确凿证据表明DAZL在靶mRNA的翻译刺激中起作用,但最近的研究表明,DAZL也可在特定mRNA的翻译抑制和转运中发挥作用。此外,除了DAZL在配子发生中已明确的功能外,最近的数据表明它在早期胚胎发育以及多能干细胞向功能性配子的分化中也发挥作用。鉴于越来越多的证据表明DAZL在各种细胞和发育过程中发挥作用,我们总结了目前已明确的DAZL在RNA生物学和发育中的生物学功能。