Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability.
Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability.
复制标题
DOI：
10.1016/j.molcel.2011.06.007
复制
发表时间：
2011-08-05
期刊：
影响因子：
16
通讯作者：
Keene JD
中科院分区：
文献类型：
--
作者：
Mukherjee N;Corcoran DL;Nusbaum JD;Reid DW;Georgiev S;Hafner M;Ascano M Jr;Tuschl T;Ohler U;Keene JD
RNA结合蛋白协调多种RNA的命运，但这些全局相互作用背后的原理仍知之甚少。我们通过整合来自多种高通量靶向技术（特别是紫外交联免疫沉淀结合高通量测序技术（PAR - CLIP）、RNA结合蛋白免疫沉淀结合芯片技术（RIP - chip）以及全转录组表达谱分析）的数据，阐明了RNA结合蛋白HuR的调控机制。每个转录本的结合位点数量、HuR结合程度以及HuR依赖的RNA稳定程度呈正相关。同时含有内含子和3′非翻译区（UTR）结合位点的前体mRNA和成熟mRNA比仅含3′ UTR或仅含内含子结合位点的转录本更稳定，这表明HuR将前体mRNA加工与成熟mRNA的稳定性联系起来。我们还观察到HuR依赖的剪接变化以及HuR在前体mRNA的多嘧啶束中的大量结合。对HuR和微小RNA（miRNA）结合位点周围空间模式的比较，为HuR依赖的对近端miRNA介导的抑制的拮抗作用提供了功能证据。我们得出结论，HuR在RNA加工的多个相互关联的步骤中协调基因表达结果。
RNA-binding proteins coordinate the fates of multiple RNAs, but the principles underlying these global interactions remain poorly understood. We elucidated regulatory mechanisms of the RNA-binding protein HuR, by integrating data from diverse high-throughput targeting technologies, specifically PAR-CLIP, RIP-chip, and whole-transcript expression profiling. The number of binding sites per transcript, degree of HuR-association, and degree of HuR-dependent RNA stabilization were positively correlated. Pre-mRNA and mature mRNA containing both intronic and 3′ UTR binding sites were more highly stabilized than transcripts with only 3′ UTR or only intronic binding sites, suggesting that HuR couples pre-mRNA processing with mature mRNA stability. We also observed HuR-dependent splicing changes and substantial binding of HuR in poly-pyrimidine tracts of pre-mRNAs. Comparison of the spatial patterns surrounding HuR and miRNA binding sites provided functional evidence for HuR-dependent antagonism of proximal miRNA-mediated repression. We conclude that HuR coordinates gene expression outcomes at multiple interconnected steps of RNA processing.
登录
查看更多内容
影响因子：
2.7
作者：
Mansfield KD;Keene JD
通讯作者：
Keene JD
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：
8
作者：
Halbeisen, R. E.;Galgano, A.;Scherrer, T.;Gerber, A. P.
通讯作者：
Gerber, A. P.
影响因子：
16.8
作者：
通讯作者：
--
影响因子：
12.3
作者：
Georgiev S;Boyle AP;Jayasurya K;Ding X;Mukherjee S;Ohler U
通讯作者：
Ohler U