Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.
Crit Rev Biochem Mol Biol. 2021 Dec;56(6):603-620. doi: 10.1080/10409238.2021.1938507. Epub 2021 Jul 7.
Translation is the set of mechanisms by which ribosomes decode genetic messages as they synthesize polypeptides of a defined amino acid sequence. While the ribosome has been honed by evolution for high-fidelity translation, errors are inevitable. Aberrant mRNAs, mRNA structure, defective ribosomes, interactions between nascent proteins and the ribosomal exit tunnel, and insufficient cellular resources, including low tRNA levels, can lead to functionally irreversible stalls. Life thus depends on quality control mechanisms that detect, disassemble and recycle stalled translation intermediates. ibosome-associated uality ontrol (RQC) recognizes aberrant ribosome states and targets their potentially toxic polypeptides for degradation. Here we review recent advances in our understanding of RQC in bacteria, fungi, and metazoans. We focus in particular on an unusual modification made to the nascent chain known as a "CAT tail", or arboxy-terminal lanine and hreonine tail, and the mechanisms by which ancient RQC proteins catalyze CAT-tail synthesis.
翻译是核糖体在合成具有特定氨基酸序列的多肽时解码遗传信息的一系列机制。虽然核糖体经过进化已经高度精确,但错误仍然不可避免。异常的 mRNA、mRNA 结构、有缺陷的核糖体、新生蛋白与核糖体出口隧道之间的相互作用以及包括低 tRNA 水平在内的有限的细胞资源会导致功能不可逆转的停滞。因此,生命依赖于质量控制机制,这些机制可以检测、拆解和回收停滞的翻译中间产物。核糖体相关质量控制(RQC)识别异常的核糖体状态,并将其潜在有毒的多肽作为降解目标。在这里,我们综述了近年来对细菌、真菌和后生动物中 RQC 的理解方面的进展。我们特别关注一种对新生链的特殊修饰,称为“CAT 尾巴”,或羧基末端丙氨酸和苏氨酸尾巴,以及古老的 RQC 蛋白催化 CAT 尾巴合成的机制。