Poly(ADP-Ribosyl)ation of hnRNP A1 Protein Controls Translational Repression in Drosophila
Poly(ADP-Ribosyl)ation of hnRNP A1 Protein Controls Translational Repression in Drosophila
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DOI：
10.1128/mcb.00207-16
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发表时间：
2016-10-01
影响因子：
5.3
通讯作者：
Tulin, Alexei V.
中科院分区：
文献类型：
--
作者：
Ji, Yingbiao;Tulin, Alexei V.
异质性核糖核蛋白(HnRNPs)的多聚(ADP-核糖基)调控着RNA在发育过程中的转录后命运。果蝇hnRNP A1，Hrp38，是生殖系干细胞维持和卵母细胞定位所必需的。Hrp38调控的信使核糖核酸靶点大多未知。我们在果蝇卵巢中鉴定了428个Hrp38相关基因转录本，其中包括翻译抑制物Nanos的mRNA。我们发现Hrp38与Nanos mRNA的3‘非翻译区(UTR)结合，该区域包含一个翻译控制元件。我们已经证明，通过dsRNA介导的Hrp38击倒以及突变潜在的Hrp38结合位点，携带Nanos 3‘UTR的荧光素酶报告的翻译被增强。我们的数据表明，聚(ADP-核糖基)抑制了Hrp38与Nanos 3‘UTR的结合，增加了体内和体外的翻译。Hrp38和Parg零突变体在胚胎早期显示异位Nanos翻译增加。我们的结论是，Hrp38抑制Nanos的翻译，而它的多聚(ADP-核糖基)解除了抑制效应，允许在卵子发生和早期胚胎发生的后部生殖质中限制Nanos的表达。
Poly(ADP-ribosyl)ation of heterogeneous nuclear ribonucleoproteins (hnRNPs) regulates the posttranscriptional fate of RNA during development. Drosophila hnRNP A1, Hrp38, is required for germ line stem cell maintenance and oocyte localization. The mRNA targets regulated by Hrp38 are mostly unknown. We identified 428 Hrp38-associated gene transcripts in the fly ovary, including mRNA of the translational repressor Nanos. We found that Hrp38 binds to the 3' untranslated region (UTR) of Nanos mRNA, which contains a translation control element. We have demonstrated that translation of the luciferase reporter bearing the Nanos 3' UTR is enhanced by dsRNA-mediated Hrp38 knockdown as well as by mutating potential Hrp38-binding sites. Our data show that poly(ADP-ribosyl) ation inhibits Hrp38 binding to the Nanos 3' UTR, increasing the translation in vivo and in vitro. hrp38 and Parg null mutants showed an increased ectopic Nanos translation early in the embryo. We conclude that Hrp38 represses Nanos translation, whereas its poly(ADP-ribosyl) ation relieves the repression effect, allowing restricted Nanos expression in the posterior germ plasm during oogenesis and early embryogenesis.