Abstract

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. Ribosome-associated Quality Control (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 Carboxy-terminal Alanine and Threonine tail, and the mechanisms by which ancient RQC proteins catalyze CAT-tail synthesis.

摘要

翻译是核糖体在合成具有确定氨基酸序列的多肽时解码遗传信息的一组机制。虽然核糖体已经通过进化进行了高保真翻译的磨练，但错误是不可避免的。异常 mRNA、mRNA 结构、有缺陷的核糖体、新生蛋白质与核糖体出口隧道之间的相互作用以及细胞资源不足（包括低 tRNA 水平）可导致功能上不可逆的停滞。因此，生命取决于检测、分解和回收停滞的翻译中间体的质量控制机制。ř ibosome相关Q uality Ç控制 (RQC) 识别异常核糖体状态并靶向其潜在毒性多肽进行降解。在这里，我们回顾了我们对细菌、真菌和后生动物 RQC 理解的最新进展。我们特别集中于对被称为“CAT尾巴”，或新生链由一个不寻常的修改Ç arboxy末端甲lanine和Ť hreonine尾和机制，通过该古RQC蛋白质催化CAT-尾合成。