Vidya Elva, Duchaine Thomas F
Goodman Cancer Institute, McGill University, Montréal, QC, Canada.
Department of Biochemistry, McGill University, Montréal, QC, Canada.
Front Genet. 2022 Mar 23;13:832547. doi: 10.3389/fgene.2022.832547. eCollection 2022.
The 5-terminal cap is a fundamental determinant of eukaryotic gene expression which facilitates cap-dependent translation and protects mRNAs from exonucleolytic degradation. Enzyme-directed hydrolysis of the cap (decapping) decisively affects mRNA expression and turnover, and is a heavily regulated event. Following the identification of the decapping holoenzyme (Dcp1/2) over two decades ago, numerous studies revealed the complexity of decapping regulation across species and cell types. A conserved set of Dcp1/2-associated proteins, implicated in decapping activation and molecular scaffolding, were identified through genetic and molecular interaction studies, and yet their exact mechanisms of action are only emerging. In this review, we discuss the prevailing models on the roles and assembly of decapping co-factors, with considerations of conservation across species and comparison across physiological contexts. We next discuss the functional convergences of decapping machineries with other RNA-protein complexes in cytoplasmic P bodies and compare current views on their impact on mRNA stability and translation. Lastly, we review the current models of decapping activation and highlight important gaps in our current understanding.
5’端帽结构是真核基因表达的一个基本决定因素，它促进帽依赖性翻译并保护mRNA免除外切核酸酶降解。酶介导的帽水解（去帽）决定性地影响mRNA的表达和周转，并且是一个受到严格调控的过程。在二十多年前鉴定出去帽全酶（Dcp1/2）之后，大量研究揭示了跨物种和细胞类型的去帽调控的复杂性。通过遗传和分子相互作用研究，鉴定出了一组与Dcp1/2相关的保守蛋白，它们参与去帽激活和分子支架作用，但其确切作用机制才刚刚开始显现。在这篇综述中，我们讨论了关于去帽辅因子的作用和组装的主流模型，同时考虑了物种间的保守性以及不同生理背景下的比较。接下来，我们讨论去帽机制与细胞质加工小体中其他RNA-蛋白质复合物的功能趋同，并比较当前关于它们对mRNA稳定性和翻译影响的观点。最后，我们回顾了当前的去帽激活模型，并强调了我们当前理解中的重要空白。
