Genome-wide analysis of Staufen-associated mRNAs identifies secondary structures that confer target specificity
Genome-wide analysis of Staufen-associated mRNAs identifies secondary structures that confer target specificity
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DOI：
10.1093/nar/gkt702
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发表时间：
2013-11-01
影响因子：
14.9
通讯作者：
Lipshitz, Howard D.
中科院分区：
文献类型：
--
作者：
Laver, John D.;Li, Xiao;Lipshitz, Howard D.
尽管有研究调查了诗道芬等双链RNA结合蛋白与RNA在体外的相互作用，但它们如何在体内实现目标特异性仍不确定。我们进行了 RNA 免疫共沉淀，然后进行微阵列分析，以鉴定早期果蝇胚胎中的 Staufen 相关 mRNA。对这些转录本的定位和功能的分析揭示了诗道芬的许多潜在的新作用。使用计算方法，我们确定了区分诗道芬目标转录本和非目标转录本的两个序列特征。首先，这些果蝇转录本以及那些与人类 Staufen1 和 2 结合的人类转录本具有比未结合转录本长 3-4 倍的 3' 非翻译区 (UTR)。其次，Staufen 结合转录物的 3'UTR 高度富集三种类型的二级结构。这些结构高精度地映射到先前在果蝇 bicoid 和人类 ARF1 3'UTR 中鉴定的 Staufen 结合区域。我们的结果提供了第一个系统的全基因组分析，显示双链 RNA 结合蛋白如何实现目标特异性。
Despite studies that have investigated the interactions of double-stranded RNA-binding proteins like Staufen with RNA in vitro, how they achieve target specificity in vivo remains uncertain. We performed RNA co-immunoprecipitations followed by microarray analysis to identify Staufen-associated mRNAs in early Drosophila embryos. Analysis of the localization and functions of these transcripts revealed a number of potentially novel roles for Staufen. Using computational methods, we identified two sequence features that distinguish Staufen's target transcripts from non-targets. First, these Drosophila transcripts, as well as those human transcripts bound by human Staufen1 and 2, have 3' untranslated regions (UTRs) that are 3-4-fold longer than unbound transcripts. Second, the 3'UTRs of Staufen-bound transcripts are highly enriched for three types of secondary structures. These structures map with high precision to previously identified Staufen-binding regions in Drosophila bicoid and human ARF1 3'UTRs. Our results provide the first systematic genome-wide analysis showing how a double-stranded RNA-binding protein achieves target specificity.