POS-1 and GLD-1 repress glp-1 translation through a conserved binding-site cluster.
POS-1 and GLD-1 repress glp-1 translation through a conserved binding-site cluster.
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DOI：
10.1091/mbc.e12-03-0216
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发表时间：
2012-12
影响因子：
3.3
通讯作者：
Ryder SP
中科院分区：
文献类型：
--
作者：
Farley BM;Ryder SP
在秀丽隐杆线虫胚胎中，抑制Notch同源物glp - 1的翻译需要POS - 1和GLD - 1。这两种蛋白质都与glp - 1的3'非翻译区（3' UTR）中的重叠元件结合。该区域内存在两个POS - 1位点，但在体内抑制作用仅需要其中一个位点。据推测，POS - 1限制了其他RNA结合蛋白进入该区域。
RNA结合蛋白（RBPs）在多种系统中协调细胞命运决定和分化。在卵母细胞发育和早期胚胎发生过程中，RNA调控至关重要，其中RBPs控制编码关键细胞命运决定因子的母体mRNA的表达。秀丽隐杆线虫的Notch同源物glp - 1协调胚胎中生殖系祖细胞增殖和前端命运决定。一个序列特异性RBPs网络对于GLP - 1翻译的模式形成是必需的。在此，我们绘制了由CCCH型串联锌指蛋白POS - 1和STAR结构域蛋白GLD - 1引导glp - 1调控的顺式调控元件图谱。我们的结果表明，这两种蛋白质通过相邻的重叠结合位点识别glp - 1的3′非翻译区，并且POS - 1的结合会排斥GLD - 1的结合。这两种因子都是抑制胚胎中glp - 1翻译所必需的，这表明它们在平行的调控途径中发挥作用。有趣的是，在glp - 1的3′非翻译区存在两个等效的POS - 1结合位点，但只有一个与翻译去抑制元件重叠的位点在体内具有功能。我们提出，POS - 1通过阻断其他RBPs接近关键调控序列来调节glp - 1 mRNA的翻译。
POS-1 and GLD-1 are required to repress the Notch homologue glp-1 translation in Caenorhabditis elegans embryos. Both proteins bind to overlapping elements in the glp-1 3' UTR. Two POS-1 sites are present within this region, but only one is required for repression in vivo. It is proposed that POS-1 restricts access of other RNA-binding proteins to this region. RNA-binding proteins (RBPs) coordinate cell fate specification and differentiation in a variety of systems. RNA regulation is critical during oocyte development and early embryogenesis, in which RBPs control expression from maternal mRNAs encoding key cell fate determinants. The Caenorhabditis elegans Notch homologue glp-1 coordinates germline progenitor cell proliferation and anterior fate specification in embryos. A network of sequence-specific RBPs is required to pattern GLP-1 translation. Here, we map the cis-regulatory elements that guide glp-1 regulation by the CCCH-type tandem zinc finger protein POS-1 and the STAR-domain protein GLD-1. Our results demonstrate that both proteins recognize the glp-1 3′ untranslated region (UTR) through adjacent, overlapping binding sites and that POS-1 binding excludes GLD-1 binding. Both factors are required to repress glp-1 translation in the embryo, suggesting that they function in parallel regulatory pathways. It is intriguing that two equivalent POS-1–binding sites are present in the glp-1 3′ UTR, but only one, which overlaps with a translational derepression element, is functional in vivo. We propose that POS-1 regulates glp-1 mRNA translation by blocking access of other RBPs to a key regulatory sequence.