Ikeuchi Ken, Izawa Toshiaki, Inada Toshifumi
Gene Regulation Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Front Genet. 2019 Jan 17;9:743. doi: 10.3389/fgene.2018.00743. eCollection 2018.
Accurate gene expression is a prerequisite for all cellular processes. Cells actively promote correct protein folding, which prevents the accumulation of abnormal and non-functional proteins. Translation elongation is the fundamental step in gene expression to ensure cellular functions, and abnormal translation arrest is recognized and removed by the quality controls. Recent studies demonstrated that ribosome plays crucial roles as a hub for gene regulation and quality controls. Ribosome-interacting factors are critical for the quality control mechanisms responding to abnormal translation arrest by targeting its products for degradation. Aberrant mRNAs are produced by errors in mRNA maturation steps and cause aberrant translation and are eliminated by the quality control system. In this review, we focus on recent progress on two quality controls, Ribosome-associated Quality Control (RQC) and No-Go Decay (NGD), for abnormal translational elongation. These quality controls recognize aberrant ribosome stalling and induce rapid degradation of aberrant polypeptides and mRNAs thereby maintaining protein homeostasis and preventing the protein aggregation.
精确的基因表达是所有细胞过程的先决条件。细胞积极促进正确的蛋白质折叠,这可防止异常和无功能蛋白质的积累。翻译延伸是基因表达中确保细胞功能的基本步骤,异常的翻译停滞会被质量控制识别并消除。最近的研究表明,核糖体作为基因调控和质量控制的中心发挥着关键作用。核糖体相互作用因子对于通过将其产物靶向降解来应对异常翻译停滞的质量控制机制至关重要。异常mRNA由mRNA成熟步骤中的错误产生,导致异常翻译,并被质量控制系统消除。在本综述中,我们关注核糖体相关质量控制(RQC)和无-go衰变(NGD)这两种针对异常翻译延伸的质量控制的最新进展。这些质量控制识别异常的核糖体停滞,并诱导异常多肽和mRNA的快速降解,从而维持蛋白质稳态并防止蛋白质聚集。