Frischmeyer Pamela A, van Hoof Ambro, O'Donnell Kathryn, Guerrerio Anthony L, Parker Roy, Dietz Harry C
Institute for Genetic Medicine, Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Science. 2002 Mar 22;295(5563):2258-61. doi: 10.1126/science.1067338.
Translation is an important mechanism to monitor the quality of messenger RNAs (mRNAs), as exemplified by the translation-dependent recognition and degradation of transcripts harboring premature termination codons (PTCs) by the nonsense-mediated mRNA decay (NMD) pathway. We demonstrate in yeast that mRNAs lacking all termination codons are as labile as nonsense transcripts. Decay of "nonstop" transcripts in yeast requires translation but is mechanistically distinguished from NMD and the major mRNA turnover pathway that requires deadenylation, decapping, and 5'-to-3' exonucleolytic decay. These data suggest that nonstop decay is initiated when the ribosome reaches the 3' terminus of the message. We demonstrate multiple physiologic sources of nonstop transcripts and conservation of their accelerated decay in mammalian cells. This process regulates the stability and expression of mRNAs that fail to signal translational termination.
翻译是监测信使核糖核酸（mRNA）质量的重要机制，无义介导的mRNA降解（NMD）途径对带有提前终止密码子（PTC）的转录本进行翻译依赖性识别和降解就例证了这一点。我们在酵母中证明，缺乏所有终止密码子的mRNA与无义转录本一样不稳定。酵母中“无终止密码子”转录本的降解需要翻译，但在机制上与NMD以及需要去腺苷酸化、脱帽和5'至3'外切核酸酶降解的主要mRNA周转途径不同。这些数据表明，当核糖体到达信使RNA的3'末端时，无终止密码子的降解就开始了。我们证明了无终止密码子转录本的多种生理来源以及它们在哺乳动物细胞中加速降解的保守性。这一过程调节了未能发出翻译终止信号的mRNA的稳定性和表达。
