Discovery of Protein-lncRNA Interactions by Integrating Large-Scale CLIP-Seq and RNA-Seq Datasets.
Discovery of Protein-lncRNA Interactions by Integrating Large-Scale CLIP-Seq and RNA-Seq Datasets.
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通过整合大规模 CLIP-Seq 和 RNA-Seq 数据集发现蛋白质-lncRNA 相互作用。
DOI：
10.3389/fbioe.2014.00088
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发表时间：
2014
影响因子：
5.7
通讯作者：
Yang JH
中科院分区：
文献类型：
--
作者：
Li JH;Liu S;Zheng LL;Wu J;Sun WJ;Wang ZL;Zhou H;Qu LH;Yang JH
长链非编码RNA（longnoncodingRNA，lncRNA）是近年来在发育、生理和病理过程中重要的调控分子。然而，大多数lncRNA的确切机制和功能在很大程度上仍然未知。交联后免疫沉淀RNA的高通量测序（CLIP-Seq）的最新进展为鉴定生物学相关蛋白质-lncRNA相互作用提供了强有力的方法。在这项研究中，通过分析来自50项独立研究生成的117个CLIP-Seq数据集的数百万个RNA结合蛋白（RBP）结合位点，我们确定了22，735个RBP-lncRNA调控关系。我们发现，一个单一的lncRNA通常会被一个或多个RBP结合和调节，它们的组合可以协调调节基因表达。我们还通过挖掘来自14种癌症类型的6000多个正常和肿瘤样本的表达谱，揭示了这些相互作用网络的表达相关性。我们对CLIP-Seq数据和全基因组关联研究数据的综合分析发现，数百种疾病相关的单核苷酸多态性位于lncRNA的RBP结合位点。最后，我们开发了交互式Web实现，以提供上述大规模数据集的可视化，分析和下载。我们的研究在识别和分析RBP-lncRNA相互作用方面迈出了重要的一步，并表明这些相互作用可能在癌症和遗传疾病中发挥关键作用。
Long non-coding RNAs (lncRNAs) are emerging as important regulatory molecules in developmental, physiological, and pathological processes. However, the precise mechanism and functions of most of lncRNAs remain largely unknown. Recent advances in high-throughput sequencing of immunoprecipitated RNAs after cross-linking (CLIP-Seq) provide powerful ways to identify biologically relevant protein–lncRNA interactions. In this study, by analyzing millions of RNA-binding protein (RBP) binding sites from 117 CLIP-Seq datasets generated by 50 independent studies, we identified 22,735 RBP–lncRNA regulatory relationships. We found that one single lncRNA will generally be bound and regulated by one or multiple RBPs, the combination of which may coordinately regulate gene expression. We also revealed the expression correlation of these interaction networks by mining expression profiles of over 6000 normal and tumor samples from 14 cancer types. Our combined analysis of CLIP-Seq data and genome-wide association studies data discovered hundreds of disease-related single nucleotide polymorphisms resided in the RBP binding sites of lncRNAs. Finally, we developed interactive web implementations to provide visualization, analysis, and downloading of the aforementioned large-scale datasets. Our study represented an important step in identification and analysis of RBP–lncRNA interactions and showed that these interactions may play crucial roles in cancer and genetic diseases.
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影响因子：
16.8
作者：
Kaneko, Syuzo;Son, Jinsook;Shen, Steven S.;Reinberg, Danny;Bonasio, Roberto
通讯作者：
Bonasio, Roberto
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
64.5
作者：
Hafner M;Landthaler M;Burger L;Khorshid M;Hausser J;Berninger P;Rothballer A;Ascano M Jr;Jungkamp AC;Munschauer M;Ulrich A;Wardle GS;Dewell S;Zavolan M;Tuschl T
通讯作者：
Tuschl T
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.