The Cardiomyocyte RNA-Binding Proteome: Links to Intermediary Metabolism and Heart Disease.
The Cardiomyocyte RNA-Binding Proteome: Links to Intermediary Metabolism and Heart Disease.
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DOI：
10.1016/j.celrep.2016.06.084
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发表时间：
2016-08-02
期刊：
影响因子：
8.8
通讯作者：
Preiss T
中科院分区：
文献类型：
--
作者：
Liao Y;Castello A;Fischer B;Leicht S;Föehr S;Frese CK;Ragan C;Kurscheid S;Pagler E;Yang H;Krijgsveld J;Hentze MW;Preiss T
RNA的功能是通过与所有生命分支中的RNA结合蛋白(RBPs)动态形成复合体来实现的。我们联合使用了两种活体蛋白质组学方法，即mRNA相互作用组学捕获和RBDmap，确定了敲打心肌细胞HL-1细胞的RBP谱系。总共产生了1,148个RBP，其中391个与所有其他可用的哺乳动物RBP谱系共享，而393个到目前为止是心肌细胞独有的。RBDmap进一步确定了368个限制性商业惯例中的568个RNA接触区。心肌细胞的mRNA相互作用组组成反映了它们独特的生物学特性。在心血管生理或疾病、线粒体功能和中间代谢中起作用的蛋白质都有很高的代表性。值得注意的是，我们确定了73种代谢酶为限制性商业惯例。RNA-酶的接触经常涉及Rossmann折叠结构域，例如两者都有，RNA结合和酶功能之间互斥或相容。我们的发现提出了以前隐藏的RNA介导的心肌细胞基因表达、生理和新陈代谢之间调控相互作用的前景。MRNA相互作用组捕获和RBDmap揭示了心肌细胞RNA结合蛋白质组1,148个限制性商业惯例，其中393个是心肌细胞所特有的。许多心脏限制性商业惯例与心脏疾病和线粒体代谢有关。代谢酶与RNA的接触往往涉及Rossmann折叠结构域，通过与生命各个分支中的RNA结合蛋白(RBP)的动态相互作用来实现RNA的功能。在这篇文章中，廖等人。介绍了小鼠心肌细胞的RBP谱系。他们的发现反映了独特的心肌细胞生物学，并提高了以前隐藏的RNA介导的基因表达、生理和新陈代谢之间调控相互作用的前景。
RNA functions through the dynamic formation of complexes with RNA-binding proteins (RBPs) in all clades of life. We determined the RBP repertoire of beating cardiomyocytic HL-1 cells by jointly employing two in vivo proteomic methods, mRNA interactome capture and RBDmap. Together, these yielded 1,148 RBPs, 391 of which are shared with all other available mammalian RBP repertoires, while 393 are thus far unique to cardiomyocytes. RBDmap further identified 568 regions of RNA contact within 368 RBPs. The cardiomyocyte mRNA interactome composition reflects their unique biology. Proteins with roles in cardiovascular physiology or disease, mitochondrial function, and intermediary metabolism are all highly represented. Notably, we identified 73 metabolic enzymes as RBPs. RNA-enzyme contacts frequently involve Rossmann fold domains with examples in evidence of both, mutual exclusivity of, or compatibility between RNA binding and enzymatic function. Our findings raise the prospect of previously hidden RNA-mediated regulatory interactions among cardiomyocyte gene expression, physiology, and metabolism. mRNA interactome capture and RBDmap reveal the cardiomyocyte RNA-binding proteome 1,148 RBPs are identified, 393 of which are thus far unique to cardiomyocytes Many cardiac RBPs have links to heart disease and mitochondrial metabolism Contacts of metabolic enzymes with RNA frequently involve Rossmann fold domains RNA functions through dynamic interactions with RNA-binding proteins (RBPs) in all clades of life. In this article, Liao et al. present the RBP repertoire of murine cardiomyocytes. Their findings reflect the unique cardiomyocyte biology and raise the prospect of previously hidden RNA-mediated regulatory interactions between gene expression, physiology, and metabolism.