Splicing of oskar RNA in the nucleus is coupled to its cytoplasmic localization

Splicing of oskar RNA in the nucleus is coupled to its cytoplasmic localization
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DOI:
10.1038/nature02521
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发表时间:
2004-04-29
期刊:
影响因子:
64.8
通讯作者:
Ephrussi, A
Ephrussi, A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hachet, O;Ephrussi, A

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oskar信使RNA定位于果蝇卵母细胞的后极对于未来胚胎的生殖系和腹部形成是必不可少的(1,2)。核穿梭蛋白Y14/Tsunagi和Mago nashi是oskar mRNA定位所必需的,并且它们与oskar mRNA共定位在卵母细胞的后极(3-5)。它们的人类同源物Y14/RBM 8和Magoh是外显子-外显子连接复合物(EJC)的核心组分(6-9)。EJC以剪接依赖性方式沉积在mRNA上,位于外显子-外显子连接点上游20 - 24个核苷酸处,与RNA序列无关(6-8)。这表明剪接在oskar mRNA定位中的可能作用,挑战了oskar 30非翻译区(3' UTR)足以进行该过程的既定概念。在这里,我们表明,剪接在第一外显子-外显子连接的奥斯卡RNA是必不可少的奥斯卡mRNA定位在后极。我们重新讨论了oskar 3' UTR是否足以用于后定位的问题,并表明携带oskar 3' UTR的不相关转录本的定位是由内源性oskar mRNA介导的。我们的研究结果揭示了一个重要的新功能剪接:信使核糖核蛋白复合物的组装和组织mRNA的细胞质定位的调节。
oskar messenger RNA localization at the posterior pole of the Drosophila oocyte is essential for germline and abdomen formation in the future embryo(1,2). The nuclear shuttling proteins Y14/Tsunagi and Mago nashi are required for oskar mRNA localization, and they co-localize with oskar mRNA at the posterior pole of the oocyte(3-5). Their human homologues, Y14/ RBM8 and Magoh, are core components of the exon - exon junction complex (EJC)(6-9). The EJC is deposited on mRNAs in a splicing-dependent manner, 20 - 24 nucleotides upstream of exon - exon junctions, independently of the RNA sequence(6-8). This indicates a possible role of splicing in oskar mRNA localization, challenging the established notion that the oskar 3 0 untranslated region (3' UTR) is sufficient for this process. Here we show that splicing at the first exon - exon junction of oskar RNA is essential for oskar mRNA localization at the posterior pole. We revisit the issue of sufficiency of the oskar 3' UTR for posterior localization and show that the localization of unrelated transcripts bearing the oskar 3' UTR is mediated by endogenous oskar mRNA. Our results reveal an important new function for splicing: regulation of messenger ribonucleoprotein complex assembly and organization for mRNA cytoplasmic localization.