From the Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
From the Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
J Biol Chem. 2013 Oct 18;288(42):30463-30472. doi: 10.1074/jbc.M113.496547. Epub 2013 Sep 6.
Maternally supplied mRNAs encode proteins that pattern early embryos in many species. In the nematode Caenorhabditis elegans, a suite of RNA-binding proteins regulates expression of maternal mRNAs during oogenesis, the oocyte to embryo transition, and early embryogenesis. To understand how these RNA-binding proteins contribute to development, it is necessary to determine how they select specific mRNA targets for regulation. OMA-1 and OMA-2 are redundant proteins required for oocyte maturation--an essential part of meiosis that prepares oocytes for fertilization. Both proteins have CCCH type tandem zinc finger RNA-binding domains. Here, we define the RNA binding specificity of OMA-1 and demonstrate that OMA-1/2 are required to repress the expression of a glp-1 3'-UTR reporter in developing oocytes. OMA-1 binds with high affinity to a conserved region of the glp-1 3'-UTR previously shown to interact with POS-1 and GLD-1, RNA-binding proteins required for glp-1 reporter repression in the posterior of fertilized embryos. Our results reveal that OMA-1 is a sequence-specific RNA-binding protein required to repress expression of maternal transcripts during oogenesis and suggest that interplay between OMA-1 and other factors for overlapping binding sites helps to coordinate the transition from oocyte to embryo.
母体供应的 mRNA 编码蛋白质,在许多物种中为早期胚胎提供模式。在线虫秀丽隐杆线虫中,一套 RNA 结合蛋白在卵母细胞发生、卵母细胞到胚胎的过渡和早期胚胎发生过程中调节母体 mRNA 的表达。为了了解这些 RNA 结合蛋白如何促进发育,有必要确定它们如何选择特定的 mRNA 靶标进行调节。OMA-1 和 OMA-2 是卵母细胞成熟所必需的冗余蛋白,卵母细胞成熟是减数分裂的一个重要部分,它使卵母细胞为受精做好准备。这两种蛋白质都具有 CCCH 型串联锌指 RNA 结合结构域。在这里,我们定义了 OMA-1 的 RNA 结合特异性,并证明 OMA-1/2 是必需的,以抑制发育中的卵母细胞中 glp-1 3'-UTR 报告基因的表达。OMA-1 与先前显示与 POS-1 和 GLD-1 相互作用的 glp-1 3'-UTR 的保守区域结合具有高亲和力,POS-1 和 GLD-1 是受精后胚胎后部抑制 glp-1 报告基因表达所必需的 RNA 结合蛋白。我们的结果表明,OMA-1 是一种序列特异性 RNA 结合蛋白,在卵母细胞发生过程中需要抑制母体转录本的表达,并表明 OMA-1 与其他因素之间的相互作用对于重叠结合位点有助于协调从卵母细胞到胚胎的过渡。