Idiosyncrasies of hnRNP A1-RNA recognition: Can binding mode influence function.
Idiosyncrasies of hnRNP A1-RNA recognition: Can binding mode influence function.
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DOI：
10.1016/j.semcdb.2018.04.001
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发表时间：
2019-03
影响因子：
7.3
通讯作者：
Tolbert BS
中科院分区：
文献类型：
--
作者：
Levengood JD;Tolbert BS
异质核核糖核蛋白 (hnRNP) 是一个多样化的 RNA 结合蛋白家族，在 RNA 代谢的大多数阶段发挥作用。其原型成员 hnRNP A1 由三个主要结构域组成：串联 N 端 RNA 识别基序 (RRM) 和 C 端本质上无序的区域。 HnRNP A1 广泛涉及基本细胞 RNA 加工事件，例如剪接、稳定性、核输出和翻译。由于其普遍性和丰富性，hnRNP A1 也经常被用来控制病毒基因表达。神经元细胞中 hnRNP A1 的 RNA 代谢功能失调会导致多种神经退行性疾病。由于 hnRNP A1 在人类病理学中的这些作用，对 hnRNP A1 的研究为开发新型疗法提供了机会，其中破坏其 RNA 结合能力是最有希望的目标。 hnRNP A1 的功能多样性反映在它与各种 RNA 靶标相互作用的复杂性质上。事实上，hnRNP A1 可以结合结构化和非结构化 RNA，其结合亲和力跨越几个量级。 hnRNP A1-RNA 复合物的可用结构也表明分子识别具有一定程度的可塑性。鉴于 hnRNP A1 的复兴，本次综述的目标是利用现有的结构生化进展作为框架来解释其广泛的 RNA 功能。
The heterogeneous nuclear ribonucleoproteins (hnRNPs) are a diverse family of RNA binding proteins that function in most stages of RNA metabolism. The prototypical member, hnRNP A1, is composed of three major domains; tandem N-terminal RNA Recognition Motifs (RRMs) and a C-terminal mostly intrinsically disordered region. HnRNP A1 is broadly implicated in basic cellular RNA processing events such as splicing, stability, nuclear export and translation. Due to its ubiquity and abundance, hnRNP A1 is also frequently usurped to control viral gene expression. Deregulation of the RNA metabolism functions of hnRNP A1 in neuronal cells contributes to several neurodegenerative disorders. Because of these roles in human pathologies, the study of hnRNP A1 provides opportunities for the development of novel therapeutics, with disruption of its RNA binding capabilities being the most promising target. The functional diversity of hnRNP A1 is reflected in the complex nature by which it interacts with various RNA targets. Indeed, hnRNP A1 binds both structured and unstructured RNAs with binding affinities that span several magnitudes. Available structures of hnRNP A1-RNA complexes also suggest a degree of plasticity in molecular recognition. Given the reinvigoration in hnRNP A1, the goal of this review is to use the available structural biochemical developments as a framework to interpret its wide-range of RNA functions.
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