Insights into RNA Biology from an Atlas of Mammalian mRNA-Binding Proteins
Insights into RNA Biology from an Atlas of Mammalian mRNA-Binding Proteins
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DOI：
10.1016/j.cell.2012.04.031
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发表时间：
2012-06-08
期刊：
影响因子：
64.5
通讯作者：
Hentze, Matthias W.
中科院分区：
文献类型：
--
作者：
Castello, Alfredo;Fischer, Bernd;Hentze, Matthias W.
RNA结合蛋白（RBP）决定RNA从合成到衰变的命运。采用两个互补的协议共价UV交联的RBP的RNA，我们描述了一个系统的，公正的，全面的方法，称为“相互作用组捕获”，以定义的mRNA相互作用组的增殖人类HeLa细胞。我们通过生物化学和统计学标准鉴定了860种有资格作为RBP的蛋白质，在先前已知的RBP基础上增加了300多种RBP，并揭示了疾病中的RBP、中间代谢的RNA结合酶、RNA结合激酶和RNA结合结构。出乎意料的是，我们发现许多蛋白质的HeLa mRNA相互作用体是高度内在的无序和丰富的短重复氨基酸基序。相互作用体捕获广泛适用于研究mRNA相互作用体组成和动态在不同的生物环境。
RNA-binding proteins (RBPs) determine RNA fate from synthesis to decay. Employing two complementary protocols for covalent UV crosslinking of RBPs to RNA, we describe a systematic, unbiased, and comprehensive approach, termed "interactome capture,'' to define the mRNA interactome of proliferating human HeLa cells. We identify 860 proteins that qualify as RBPs by biochemical and statistical criteria, adding more than 300 RBPs to those previously known and shedding light on RBPs in disease, RNA-binding enzymes of intermediary metabolism, RNA-binding kinases, and RNA-binding architectures. Unexpectedly, we find that many proteins of the HeLa mRNA interactome are highly intrinsically disordered and enriched in short repetitive amino acid motifs. Interactome capture is broadly applicable to study mRNA interactome composition and dynamics in varied biological settings.