Integrative genome-wide analysis reveals cooperative regulation of alternative splicing by hnRNP proteins.
Integrative genome-wide analysis reveals cooperative regulation of alternative splicing by hnRNP proteins.
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DOI：
10.1016/j.celrep.2012.02.001
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发表时间：
2012-02-23
期刊：
影响因子：
8.8
通讯作者：
Yeo GW
中科院分区：
文献类型：
--
作者：
Huelga SC;Vu AQ;Arnold JD;Liang TY;Liu PP;Yan BY;Donohue JP;Shiue L;Hoon S;Brenner S;Ares M Jr;Yeo GW
了解RNA结合蛋白如何控制剪接密码是人类生物学和疾病的基础。在这里，我们提出了一个全面的研究，以阐明异质核核糖核颗粒（hnRNP）蛋白，其中最丰富的RNA结合蛋白，协调调节人类细胞中的替代前mRNA剪接（AS）。使用剪接敏感的微阵列，交联和免疫沉淀加上高通量测序，和cDNA测序，我们发现，超过一半的AS事件是由多种hnRNP蛋白调节，并且一些hnRNP蛋白的组合表现出显着的协同作用，而其他人则表现出拮抗作用。我们的分析揭示了位置依赖性RNA剪接图，体内共有结合位点，hnRNP蛋白之间令人惊讶的交叉和自动调节水平，以及hnRNP蛋白对数十种其他RNA结合蛋白和与癌症相关的基因的协调调节。我们的研究结果定义了hnRNP蛋白及其剪接靶点之间前所未有的复杂性和补偿关系，这些蛋白可能赋予细胞鲁棒性。
Understanding how RNA binding proteins control the splicing code is fundamental to human biology and disease. Here we present a comprehensive study to elucidate how heterogeneous nuclear ribonucleoparticle (hnRNP) proteins, among the most abundant RNA binding proteins, coordinate to regulate alternative pre-mRNA splicing (AS) in human cells. Using splicing-sensitive microarrays, cross-linking and immunoprecipitation coupled with high-throughput sequencing, and cDNA sequencing, we find that more than half of all AS events are regulated by multiple hnRNP proteins, and that some combinations of hnRNP proteins exhibit significant synergy, whereas others act antagonistically. Our analyses reveal position-dependent RNA splicing maps, in vivo consensus binding sites, a surprising level of cross- and auto-regulation among hnRNP proteins, and the coordinated regulation by hnRNP proteins of dozens of other RNA binding proteins and genes associated with cancer. Our findings define an unprecedented degree of complexity and compensatory relationships among hnRNP proteins and their splicing targets that likely confer robustness to cells.
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DOI：
10.1158/1541-7786.mcr-09-0528
发表时间：
2010-07
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Lapuk A;Marr H;Jakkula L;Pedro H;Bhattacharya S;Purdom E;Hu Z;Simpson K;Pachter L;Durinck S;Wang N;Parvin B;Fontenay G;Speed T;Garbe J;Stampfer M;Bayandorian H;Dorton S;Clark TA;Schweitzer A;Wyrobek A;Feiler H;Spellman P;Conboy J;Gray JW
通讯作者：
Gray JW
影响因子：
48
作者：
Katz, Yarden;Wang, Eric T.;Airoldi, Edoardo M.;Burge, Christopher B.
通讯作者：
Burge, Christopher B.
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
DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
16
作者：
Blanchette, Marco;Green, Richard E.;Rio, Donald C.
通讯作者：
Rio, Donald C.