Center for Reproductive Sciences, University of California, San Francisco, CA, 94143, USA.
USA Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, 94143, USA.
Nat Commun. 2020 Mar 13;11(1):1399. doi: 10.1038/s41467-020-15209-9.
Deleted in azoospermia-like (DAZL) is an RNA-binding protein critical for gamete development. In full-grown oocytes, the DAZL protein increases 4-fold during reentry into the meiotic cell cycle. Here, we have investigated the functional significance of this accumulation at a genome-wide level. Depletion of DAZL causes a block in maturation and widespread disruption in the pattern of ribosome loading on maternal transcripts. In addition to decreased translation, DAZL depletion also causes translational activation of a distinct subset of mRNAs both in quiescent and maturing oocytes, a function recapitulated with YFP-3'UTR reporters. DAZL binds to mRNAs whose translation is both repressed and activated during maturation. Injection of recombinant DAZL protein in DAZL-depleted oocytes rescues the translation and maturation to MII. Mutagenesis of putative DAZL-binding sites in these mRNAs mimics the effect of DAZL depletion. These findings demonstrate that DAZL regulates translation of maternal mRNAs, functioning both as the translational repressor and activator during oocyte maturation.
缺失于无精子症样（DAZL）是一种对配子发生至关重要的 RNA 结合蛋白。在成熟的卵母细胞中，DAZL 蛋白在重新进入减数分裂细胞周期时增加 4 倍。在这里，我们从全基因组水平研究了这种积累的功能意义。DAZL 的耗竭导致成熟受阻，并广泛破坏母本转录物上核糖体加载的模式。除了翻译减少之外，DAZL 耗竭还导致静止和成熟卵母细胞中一组不同的 mRNA 的翻译激活，这一功能可以用 YFP-3'UTR 报告器重现。DAZL 结合到在成熟过程中翻译受到抑制和激活的 mRNA。在 DAZL 耗竭的卵母细胞中注射重组 DAZL 蛋白可挽救翻译并使其成熟至 MII。这些 mRNA 中假定的 DAZL 结合位点的突变模拟了 DAZL 耗竭的效果。这些发现表明，DAZL 调节母本 mRNA 的翻译，在卵母细胞成熟过程中既是翻译抑制剂又是激活剂。
