The expanding universe of ribonucleoproteins: of novel RNA-binding proteins and unconventional interactions.
The expanding universe of ribonucleoproteins: of novel RNA-binding proteins and unconventional interactions.
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DOI：
10.1007/s00424-016-1819-4
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Medenbach J
中科院分区：
文献类型：
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作者：
Beckmann BM;Castello A;Medenbach J
基因表达的转录后调控在几乎所有的细胞过程中起着关键作用。调节主要通过RNA结合蛋白（RBP）发生，其识别RNA元件并形成核糖核蛋白（RNP）以控制RNA从合成到衰变的代谢。最近，由于RNA相互作用组捕获等方法的进步，限制性商业惯例的全部内容得到了显著扩展。新发现的RNA结合剂参与多种生物过程，属于广泛的蛋白质家族，其中许多具有酶活性。这表明RNA生物学和其他原则上不相关的细胞功能（如中间代谢）之间存在广泛的串扰。出乎意料的是，数百种新的RBP不包含可识别的RNA结合结构域（RBD），这就提出了它们如何与RNA相互作用的问题。尽管RNA具有许多功能，但我们对RNP的理解仍然主要受蛋白质中心观点的支配，导致蛋白质进化为结合和调节RNA，而不是相反。然而，由RNA驱动的相互作用机制（RNA决定的RNP）形成的RNP是丰富的，并为许多RNA相互作用蛋白中令人惊讶的缺乏经典RBD提供了另一种解释。此外，RNA可以作为支架来协调和组织蛋白质网络，并直接控制它们的活性，这表明核酸可能在许多细胞过程中发挥重要的调节作用，包括代谢。
Post-transcriptional regulation of gene expression plays a critical role in almost all cellular processes. Regulation occurs mostly by RNA-binding proteins (RBPs) that recognise RNA elements and form ribonucleoproteins (RNPs) to control RNA metabolism from synthesis to decay. Recently, the repertoire of RBPs was significantly expanded owing to methodological advances such as RNA interactome capture. The newly identified RNA binders are involved in diverse biological processes and belong to a broad spectrum of protein families, many of them exhibiting enzymatic activities. This suggests the existence of an extensive crosstalk between RNA biology and other, in principle unrelated, cell functions such as intermediary metabolism. Unexpectedly, hundreds of new RBPs do not contain identifiable RNA-binding domains (RBDs), raising the question of how they interact with RNA. Despite the many functions that have been attributed to RNA, our understanding of RNPs is still mostly governed by a rather protein-centric view, leading to the idea that proteins have evolved to bind to and regulate RNA and not vice versa. However, RNPs formed by an RNA-driven interaction mechanism (RNA-determined RNPs) are abundant and offer an alternative explanation for the surprising lack of classical RBDs in many RNA-interacting proteins. Moreover, RNAs can act as scaffolds to orchestrate and organise protein networks and directly control their activity, suggesting that nucleic acids might play an important regulatory role in many cellular processes, including metabolism.