Computational prediction of RNA structural motifs involved in posttranscriptional regulatory processes

Computational prediction of RNA structural motifs involved in posttranscriptional regulatory processes
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DOI:
10.1073/pnas.0803169105
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发表时间:
2008-09-30
影响因子:
11.1
通讯作者:
Segal, Eran
Segal, Eran
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Rabani, Michal;Kertesz, Michael;Segal, Eran

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信使RNA分子受到严格的调控,主要是通过与蛋白质和其他RNA的相互作用,但赋予这种相互作用的特异性的机制却鲜为人知。然而,很明显,这种特异性是由mRNA的核苷酸序列和二级结构决定的。在这里,我们开发了RNAproo,这是一种高效的计算工具,用于识别mRNAs中参与指定转录后调控的结构元素。通过分析mRNA衰减率的实验数据,我们确定了快衰期和慢衰期mRNAs中的共同结构元素,并将它们与几种RNA结合蛋白的结合偏好联系起来。我们还预测了在小鼠神经元和苍蝇胚胎中具有共同亚细胞定位的一组mRNAs中的结构元素。最后,通过分析前microRNA茎环,我们识别了动物和植物前microRNA之间的结构差异,这为深入了解microRNA的生物发生机制提供了见解。综上所述,我们的结果揭示了一组RNA中尚未探索的转录后调控层,因此是更好地理解RNA分子中传达的调控信息的重要一步。我们新的RNA基序发现工具在网上可用。
Messenger RNA molecules are tightly regulated, mostly through interactions with proteins and other RNAs, but the mechanisms that confer the specificity of such interactions are poorly understood. It is clear, however, that this specificity is determined by both the nucleotide sequence and secondary structure of the mRNA. Here, we develop RNApromo, an efficient computational tool for identifying structural elements within mRNAs that are involved in specifying posttranscriptional regulations. By analyzing experimental data on mRNA decay rates, we identify common structural elements in fast-decaying and slow-decaying mRNAs and link them with binding preferences of several RNA binding proteins. We also predict structural elements in sets of mRNAs with common subcellular localization in mouse neurons and fly embryos. Finally, by analyzing premicroRNA stem-loops, we identify structural differences between pre-microRNAs of animals and plants, which provide insights into the mechanism of microRNA biogenesis. Together, our results reveal unexplored layers of posttranscriptional regulations in groups of RNAs and are therefore an important step toward a better understanding of the regulatory information conveyed within RNA molecules. Our new RNA motif discovery tool is available online.