Tranposable elements modulate human mRNAs and lncRNAs via specific RNA-protein interactions.. Homo sapiens

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, studied a collection of CLIP-Seq (CrossLinked ImmunoPrecipitation) experiments mapping the RNA binding sites for a diverse set of 46 human proteins across 68 experiments to explore the role of TEs in post-transcriptional regulation genome-wide via RNA-protein interactions. We detected widespread interactions between RNA binding proteins (RBPs) and various families of TE-derived sequence in the CLIP-Seq data. Alignment coverage clustered on specific positions of the TE consensus sequences, illuminating a diversity of TE-specific motifs for many RBPs. Evidence of binding and conservation of these motifs in the nonrepetitive transcriptome suggest that TEs have appropriated existing sequence preferences of the RBP. Upon depletion of the RBPs, transcripts possessing TE-derived binding sites were similarly regulated as those bound in nonrepetitive sequence. However, in a few cases the effect of RBP binding depended on the specific TE family bound—e.g., the ubiquitously expressed RBP HuR conferred opposite effects on stability to transcripts when bound to Alu elements versus other families. Our meta-analysis suggests a widespread role for TEs in shaping RNA-protein regulatory networks in the human genome. Overall design: HuR formaldehyde RIP-Seq in K562 cells, with RIP and input sequenced in triplicate.

转座因子（Transposable Elements, TEs）对人类基因组中转录调控网络的演化产生了极为深远的影响。已有研究在特定场景中观察到由转座因子衍生序列介导的人类基因转录后调控现象，但该过程仍缺乏系统性与全面性的探究。
本研究对一组CLIP-Seq（交联免疫沉淀，CrossLinked ImmunoPrecipitation）实验数据集进行了分析：该数据集涵盖68组实验，用于绘制46种不同人类蛋白的RNA结合位点，借此通过RNA-蛋白质相互作用在全基因组范围内探究转座因子在转录后调控中发挥的作用。
我们在CLIP-Seq数据中检测到RNA结合蛋白（RNA Binding Proteins, RBPs）与多类转座因子衍生序列之间存在广泛的相互作用。
比对覆盖度聚集于转座因子共识序列的特定位点，揭示了多种RBPs所结合的转座因子特异性基序的多样性。
这些基序在非重复转录组中存在结合与保守性的证据表明，转座因子已适配了RBPs原本的序列结合偏好性。
在RBPs被敲低后，携带转座因子衍生结合位点的转录本与结合于非重复序列的转录本受到了相似的调控。
但在少数情形中，RBPs结合的调控效应取决于其所结合的转座因子家族类型：例如，普遍表达的RBPs HuR在结合Alu元件（Alu elements）与其他转座因子家族时，会对转录本稳定性产生截然相反的调控效果。
本项荟萃分析表明，转座因子在塑造人类基因组内的RNA-蛋白质调控网络中发挥着广泛的作用。
实验整体设计：在K562细胞系中开展HuR甲醛交联RNA免疫沉淀测序（RIP-Seq），其中RIP样本与输入样本均进行了三联重复测序。