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内源性人核糖核蛋白复合物的系统发现。

Systematic Discovery of Endogenous Human Ribonucleoprotein Complexes.

机构信息

Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA; Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX 78712, USA; Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.

Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA; Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX 78712, USA; Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.

出版信息

Cell Rep. 2019 Oct 29;29(5):1351-1368.e5. doi: 10.1016/j.celrep.2019.09.060.

Abstract

RNA-binding proteins (RBPs) play essential roles in biology and are frequently associated with human disease. Although recent studies have systematically identified individual RNA-binding proteins, their higher-order assembly into ribonucleoprotein (RNP) complexes has not been systematically investigated. Here, we describe a proteomics method for systematic identification of RNP complexes in human cells. We identify 1,428 protein complexes that associate with RNA, indicating that more than 20% of known human protein complexes contain RNA. To explore the role of RNA in the assembly of each complex, we identify complexes that dissociate, change composition, or form stable protein-only complexes in the absence of RNA. We use our method to systematically identify cell-type-specific RNA-associated proteins in mouse embryonic stem cells and finally, distribute our resource, rna.MAP, in an easy-to-use online interface (rna.proteincomplexes.org). Our system thus provides a methodology for explorations across human tissues, disease states, and throughout all domains of life.

摘要

RNA 结合蛋白(RBPs)在生物学中发挥着重要作用,并且经常与人类疾病有关。尽管最近的研究已经系统地鉴定了单个 RNA 结合蛋白,但它们的更高阶组装成核糖核蛋白(RNP)复合物尚未被系统地研究。在这里,我们描述了一种用于系统鉴定人类细胞中 RNP 复合物的蛋白质组学方法。我们鉴定了 1428 个与 RNA 相关的蛋白质复合物,表明超过 20%的已知人类蛋白质复合物包含 RNA。为了探索 RNA 在每个复合物组装中的作用,我们鉴定了在没有 RNA 的情况下会解离、改变组成或形成稳定的仅蛋白质复合物的复合物。我们使用我们的方法在小鼠胚胎干细胞中系统地鉴定了细胞类型特异性的 RNA 相关蛋白,最后,我们将我们的资源 rna.MAP 以易于使用的在线界面(rna.proteincomplexes.org)发布。因此,我们的系统为探索人类组织、疾病状态以及所有生命领域提供了一种方法。

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