Rodnina Marina V
Department of Physical Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, 37077, Germany.
Protein Sci. 2016 Aug;25(8):1390-406. doi: 10.1002/pro.2950. Epub 2016 Jun 8.
The cellular proteome is shaped by the combined activities of the gene expression and quality control machineries. While transcription plays an undoubtedly important role, in recent years also translation emerged as a key step that defines the composition and quality of the proteome and the functional activity of proteins in the cell. Among the different post-transcriptional control mechanisms, translation initiation and elongation provide multiple checkpoints that can affect translational efficiency. A multitude of specific signals in mRNAs can determine the frequency of translation initiation, choice of the open reading frame, global and local elongation velocities, and the folding of the emerging protein. In addition to specific signatures in the mRNAs, also variations in the global pools of translation components, including ribosomes, tRNAs, mRNAs, and translation factors can alter translational efficiencies. The cellular outcomes of phenomena such as mRNA codon bias are sometimes difficult to understand due to the staggering complexity of covariates that affect codon usage, translation, and protein folding. Here we summarize the experimental evidence on how the ribosome-together with the other components of the translational machinery-can alter translational efficiencies of mRNA at the initiation and elongation stages and how translation velocity affects protein folding. We seek to explain these findings in the context of mechanistic work on the ribosome. The results argue in favour of a new understanding of translation control as a hub that links mRNA homeostasis to production and quality control of proteins in the cell.
细胞蛋白质组是由基因表达和质量控制机制的联合活动塑造而成的。虽然转录无疑起着重要作用，但近年来翻译也成为了一个关键步骤，它决定了蛋白质组的组成和质量以及细胞中蛋白质的功能活性。在不同的转录后控制机制中，翻译起始和延伸提供了多个可影响翻译效率的检查点。mRNA中的众多特定信号可决定翻译起始频率、开放阅读框的选择、全局和局部延伸速度以及新生蛋白质的折叠。除了mRNA中的特定特征外，翻译组件的全局库（包括核糖体、tRNA、mRNA和翻译因子）的变化也会改变翻译效率。由于影响密码子使用、翻译和蛋白质折叠的协变量极其复杂，诸如mRNA密码子偏好等现象的细胞结果有时难以理解。在这里，我们总结了关于核糖体以及翻译机制的其他组件如何在起始和延伸阶段改变mRNA翻译效率以及翻译速度如何影响蛋白质折叠的实验证据。我们试图在核糖体机制研究的背景下解释这些发现。结果支持将翻译控制重新理解为一个将mRNA稳态与细胞中蛋白质的产生和质量控制联系起来的枢纽。
