Department of Biophysics I, University of Regensburg, 93053, Regensburg, Germany.
Curr Opin Struct Biol. 2019 Dec;59:115-123. doi: 10.1016/j.sbi.2019.07.009. Epub 2019 Aug 29.
Eukaryotic mRNAs contain a 5' cap structure that protects the transcript against rapid exonucleolytic degradation. The regulation of cellular mRNA levels therefore depends on a precise control of the mRNA decapping pathways. The major mRNA decapping enzyme in eukaryotic cells is Dcp2. It is regulated by interactions with several activators, including Dcp1, Edc1, and Edc3, as well as by an autoinhibition mechanism. The structural and mechanistical characterization of Dcp2 complexes has long been impeded by the high flexibility and dynamic nature of the enzyme. Here we review recent insights into the catalytically active conformation of the mRNA decapping complex, the mode of action of decapping activators and the large interactions network that Dcp2 is embedded in.
真核生物的 mRNA 含有 5' 帽结构,可保护转录本免受快速核酸外切降解的影响。因此,细胞 mRNA 水平的调节取决于对 mRNA 去帽途径的精确控制。真核细胞中的主要 mRNA 去帽酶是 Dcp2。它受与几个激活剂的相互作用调节,包括 Dcp1、Edc1 和 Edc3,以及自身抑制机制。Dcp2 复合物的结构和机制特征长期以来一直受到酶的高度灵活性和动态性质的阻碍。本文综述了近年来对 mRNA 去帽复合物催化活性构象、去帽激活剂作用模式以及 Dcp2 嵌入的大相互作用网络的深入了解。