Division of Life Sciences, Incheon National University, Incheon 22012, Korea.
Department of Medical Science, Catholic Kwandong University College of Medicine, Incheon 22711, Korea.
BMB Rep. 2022 Mar;55(3):125-135. doi: 10.5483/BMBRep.2022.55.3.188.
Continuously renewing the proteome, translation is exquisitely controlled by a number of dedicated factors that interact with the ribosome. The RNA helicase DDX3 belonging to the DEAD box family has emerged as one of the critical regulators of translation, the failure of which is frequently observed in a wide range of proliferative, degenerative, and infectious diseases in humans. DDX3 unwinds double-stranded RNA molecules with coupled ATP hydrolysis and thereby remodels complex RNA structures present in various protein-coding and noncoding RNAs. By interacting with specific features on messenger RNAs (mRNAs) and 18S ribosomal RNA (rRNA), DDX3 facilitates translation, while repressing it under certain conditions. We review recent findings underlying these properties of DDX3 in diverse modes of translation, such as cap-dependent and cap-independent translation initiation, usage of upstream open reading frames, and stress-induced ribonucleoprotein granule formation. We further discuss how disease-associated DDX3 variants alter the translation landscape in the cell. [BMB Reports 2022; 55(3): 125-135].
不断更新蛋白质组，翻译受到许多专门的因子的精细控制，这些因子与核糖体相互作用。属于 DEAD 盒家族的 RNA 解旋酶 DDX3 已成为翻译的关键调节因子之一，在人类的多种增殖性、退行性和传染性疾病中，经常观察到其功能失效。DDX3 通过与 ATP 水解偶联解开双链 RNA 分子，从而重塑各种编码蛋白和非编码 RNA 中存在的复杂 RNA 结构。DDX3 通过与信使 RNA（mRNA）和 18S 核糖体 RNA（rRNA）上的特定特征相互作用，促进翻译，而在某些条件下则抑制翻译。我们回顾了 DDX3 在不同翻译模式下的这些特性的最新发现，例如帽依赖性和帽非依赖性翻译起始、上游开放阅读框的使用以及应激诱导的核糖核蛋白颗粒形成。我们进一步讨论了与疾病相关的 DDX3 变体如何改变细胞中的翻译景观。[BMB 报告 2022；55(3): 125-135]。
