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The Cardiomyocyte RNA-Binding Proteome: Links to Intermediary Metabolism and Heart Disease

机译:心肌RNA结合蛋白质组:链接到中间代谢和心脏病。

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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.
机译:RNA通过在生活的所有进化枝中动态形成与RNA结合蛋白(RBP)形成的复合物而起作用。我们通过联合采用两种体内蛋白质组学方法,即mRNA相互作用组捕获和RBDmap,确定了跳动的心肌HL-1细胞的RBP组成。这些合在一起产生了1,148个RBP,其中391个与所有其他可用的哺乳动物RBP组成部分共享,而迄今为止,393个是心肌细胞所独有的。 RBDmap进一步鉴定了368个RBP内的568个RNA接触区域。心肌mRNA相互作用组的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得到了高度体现。值得注意的是,我们确定了73种代谢酶作为RBP。 RNA酶接触经常涉及Rossmann折叠结构域,并举例说明RNA结合与酶功能的互斥性或相容性。我们的发现提高了心肌细胞基因表达,生理和代谢之间先前隐藏的RNA介导的调控相互作用的前景。

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