Transposable elements modulate human RNA abundance and splicing via specific RNA-protein interactions.
Transposable elements modulate human RNA abundance and splicing via specific RNA-protein interactions.
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DOI：
10.1186/s13059-014-0537-5
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发表时间：
2014-12-03
期刊：
影响因子：
12.3
通讯作者：
Rinn JL
中科院分区：
文献类型：
--
作者：
Kelley DR;Hendrickson DG;Tenen D;Rinn JL
转座因子（Transposable elements，TE）对人类基因组中转录调控网络的进化具有重要影响。TE衍生序列对人类基因的转录后调控已经在特定的背景下被观察到，但还有待于系统和全面的研究。在这里，我们研究了75个CLIP-Seq实验的集合，这些实验绘制了51种不同人类蛋白质的RNA结合位点，以探索TE通过RNA-蛋白质相互作用在人类mRNA和lncRNA转录后调控中的作用。我们在CLIP-Seq数据中检测到RNA结合蛋白（RBP）和许多TE衍生序列家族之间的广泛相互作用。此外，比对覆盖率在TE共有序列的特定位置上达到峰值，从而阐明了TE特异性RBP结合基序的多样性。在非重复转录组中这些基序的结合和保守的证据表明，TE通常已经占用了RBP的现有序列偏好。许多RBPs的消耗试验表明，TE衍生的结合位点影响转录丰度和剪接类似于非重复位点。然而，在少数情况下，RBP结合的效果取决于结合的特定TE家族;例如，普遍表达的RBP HuR赋予转录物稳定性，除非结合到Alu元件。我们的荟萃分析表明，TE在塑造人类基因组中的RNA-蛋白质调控网络中发挥着广泛的作用。本文的在线版本（doi：10.1186/s13059-014-0537-5）包含补充材料，可供授权用户使用。
Transposable elements (TEs) have significantly influenced the evolution of transcriptional regulatory networks in the human genome. Post-transcriptional regulation of human genes by TE-derived sequences has been observed in specific contexts, but has yet to be systematically and comprehensively investigated. Here, we study a collection of 75 CLIP-Seq experiments mapping the RNA binding sites for a diverse set of 51 human proteins to explore the role of TEs in post-transcriptional regulation of human mRNAs and lncRNAs via RNA-protein interactions. We detect widespread interactions between RNA binding proteins (RBPs) and many families of TE-derived sequence in the CLIP-Seq data. Further, alignment coverage peaks on specific positions of the TE consensus sequences, illuminating a diversity of TE-specific RBP binding motifs. Evidence of binding and conservation of these motifs in the nonrepetitive transcriptome suggests that TEs have generally appropriated existing sequence preferences of the RBPs. Depletion assays for numerous RBPs show that TE-derived binding sites affect transcript abundance and splicing similarly to nonrepetitive sites. However, in a few cases the effect of RBP binding depends on the specific TE family bound; for example, the ubiquitously expressed RBP HuR confers transcript stability unless bound to an Alu element. Our meta-analysis suggests a widespread role for TEs in shaping RNA-protein regulatory networks in the human genome. The online version of this article (doi:10.1186/s13059-014-0537-5) contains supplementary material, which is available to authorized users.
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