Metabolic Enzymes Enjoying New Partnerships as RNA-Binding Proteins.
Metabolic Enzymes Enjoying New Partnerships as RNA-Binding Proteins.
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DOI：
10.1016/j.tem.2015.09.012
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Preiss T
中科院分区：
文献类型：
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作者：
Castello A;Hentze MW;Preiss T
在过去的世纪里，很少有生物学领域像我们对中间代谢途径的理解那样进步。最初被认为在基因调控方面不重要，现在已知关键的细胞命运变化、细胞分化或恶性转化涉及“代谢重塑”，其中许多代谢酶基因的表达发生深刻变化。本文综述了近年来发现的许多代谢酶的RNA结合活性。我们讨论了反馈基因调控（“兼职”）和/或在控制酶的功能，这意想不到的第二个活动可能发挥的作用。我们还考虑了代谢驱动的翻译后修饰如何调节酶-RNA相互作用。因此，RNA作为代谢酶的新伙伴出现，其深远的可能后果有待于未来解开。代谢的遗传控制目前在转录和表观遗传学水平上得到最好的理解。只有有限的信息是可利用的转录后调节代谢。虽然以前已知一些代谢酶在生理学相关背景下作为RNA结合蛋白，但最近的发现强调了属于广泛途径的几十种代谢酶在活的哺乳动物细胞中表现出RNA结合活性。丰富的RNA-酶相互作用可能表明RNA在影响酶功能方面的新作用，例如，作为竞争性抑制剂或变构调节剂。RNA作为酶复合物组装支架的功能也是可以想象的，这对我们理解细胞如何组织和控制代谢通量具有潜在的广泛意义。最后，酶可以作为（m）RNA的调节剂，如乌头酸酶/IRP 1和GAPDH。
In the past century, few areas of biology advanced as much as our understanding of the pathways of intermediary metabolism. Initially considered unimportant in terms of gene regulation, crucial cellular fate changes, cell differentiation, or malignant transformation are now known to involve ‘metabolic remodeling’ with profound changes in the expression of many metabolic enzyme genes. This review focuses on the recent identification of RNA-binding activity of numerous metabolic enzymes. We discuss possible roles of this unexpected second activity in feedback gene regulation (‘moonlighting’) and/or in the control of enzymatic function. We also consider how metabolism-driven post-translational modifications could regulate enzyme–RNA interactions. Thus, RNA emerges as a new partner of metabolic enzymes with far-reaching possible consequences to be unraveled in the future. Genetic control of metabolism is currently best understood at the level of transcription and epigenetics. Only limited information is available on post-transcriptional regulation of metabolism. While a few metabolic enzymes were previously known to moonlight as RNA-binding proteins in physiologically relevant contexts, recent discoveries highlight that several dozen of metabolic enzymes belonging to a wide spectrum of pathways exhibit RNA-binding activity in living mammalian cells. Abundant RNA–enzyme interactions might suggest novel roles of RNA in affecting enzyme function, for instance, as competitive inhibitors or allosteric regulators. A function of RNA as assembly scaffold for enzyme complexes is also conceivable, with potentially wide-ranging implications for our understanding of how cells organize and control metabolic flux. Finally, enzymes can moonlight as regulators of (m)RNAs, as exemplified by aconitase/IRP1 and GAPDH.