RNA-binding protein GLD-1/quaking genetically interacts with the mir-35 and the let-7 miRNA pathways in Caenorhabditis elegans.
RNA-binding protein GLD-1/quaking genetically interacts with the mir-35 and the let-7 miRNA pathways in Caenorhabditis elegans.
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DOI：
10.1098/rsob.130151
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发表时间：
2013-11-20
期刊：
影响因子：
5.8
通讯作者：
Gartner A
中科院分区：
文献类型：
--
作者：
Akay A;Craig A;Lehrbach N;Larance M;Pourkarimi E;Wright JE;Lamond A;Miska E;Gartner A
信使RNA的翻译受RNA结合蛋白和称为microRNA的小的非编码RNA的调节。尽管我们知道大多数RNA结合蛋白和microRNA调节信使RNA表达，但两者之间相互作用的证据仍然难以捉摸。RNA结合蛋白GLD-1作为一个翻译阻遏物的作用在秀丽隐杆线虫生殖系发育和维持过程中得到了很好的研究。GLD-1在体细胞发育过程中的可能功能以及GLD-1如何作为翻译阻遏物的机制尚不清楚。它的人类同源物，震颤（QKI），是胚胎发育所必需的。在此，我们报道了C.线虫影响多种microRNA途径，并与microRNA功能所需的蛋白质相互作用。利用全基因组RNAi筛选，我们发现nhl-2和vig-1，两种已知的miRNA功能调节剂，与GLD-1在遗传上相互作用。GLD-1突变增强了由mir-35和let-7家族突变体在体细胞发育过程中赋予的多种表型。我们在细胞培养中使用稳定同位素标记氨基酸，全面分析let-7和gld-1在动物发育过程中赋予蛋白质组的变化。我们确定了组蛋白mRNA结合蛋白CDL-1是，在一定程度上，负责let-7和gld-1突变体中观察到的表型。GLD-1与miRNA介导的基因调控之间的联系进一步得到了其与ALG-1、CGH-1和PAB-1（参与miRNA调控的蛋白质）的生物化学相互作用的支持。总体而言，我们已经发现了GLD-1和miRNA通路之间的遗传和生化相互作用。
Messenger RNA translation is regulated by RNA-binding proteins and small non-coding RNAs called microRNAs. Even though we know the majority of RNA-binding proteins and microRNAs that regulate messenger RNA expression, evidence of interactions between the two remain elusive. The role of the RNA-binding protein GLD-1 as a translational repressor is well studied during Caenorhabditis elegans germline development and maintenance. Possible functions of GLD-1 during somatic development and the mechanism of how GLD-1 acts as a translational repressor are not known. Its human homologue, quaking (QKI), is essential for embryonic development. Here, we report that the RNA-binding protein GLD-1 in C. elegans affects multiple microRNA pathways and interacts with proteins required for microRNA function. Using genome-wide RNAi screening, we found that nhl-2 and vig-1, two known modulators of miRNA function, genetically interact with GLD-1. gld-1 mutations enhance multiple phenotypes conferred by mir-35 and let-7 family mutants during somatic development. We used stable isotope labelling with amino acids in cell culture to globally analyse the changes in the proteome conferred by let-7 and gld-1 during animal development. We identified the histone mRNA-binding protein CDL-1 to be, in part, responsible for the phenotypes observed in let-7 and gld-1 mutants. The link between GLD-1 and miRNA-mediated gene regulation is further supported by its biochemical interaction with ALG-1, CGH-1 and PAB-1, proteins implicated in miRNA regulation. Overall, we have uncovered genetic and biochemical interactions between GLD-1 and miRNA pathways.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
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影响因子：
48
作者：
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通讯作者：
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影响因子：
48
作者：
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通讯作者：
Ambros, Victor
影响因子：
56.9
作者：
AMBROS, V;HORVITZ, HR
通讯作者：
HORVITZ, HR
影响因子：
48
作者：
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通讯作者：
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