Mitchell Philip, Tollervey David
Wellcome Trust Centre for Cell Biology, Institute for Cell and Molecular Biology, King's Buildings, University of Edinburgh, EH9 3JR, United Kingdom.
Mol Cell. 2003 May;11(5):1405-13. doi: 10.1016/s1097-2765(03)00190-4.
Eukaryotic mRNAs containing premature termination codons are subjected to accelerated turnover, known as nonsense-mediated decay (NMD). Recognition of translation termination events as premature requires a surveillance complex, which includes the RNA helicase Upf1p. In Saccharomyces cerevisiae, NMD provokes rapid decapping followed by 5'-->3' exonucleolytic decay. Here we report an alternative, decapping-independent NMD pathway involving deadenylation and subsequent 3'-->5' exonucleolytic decay. Accelerated turnover via this pathway required Upf1p and was blocked by the translation inhibitor cycloheximide. Degradation of the deadenylated mRNA required the Rrp4p and Ski7p components of the cytoplasmic exosome complex, as well as the putative RNA helicase Ski2p. We conclude that recognition of NMD substrates by the Upf surveillance complex can target mRNAs to rapid deadenylation and exosome-mediated degradation.
含有提前终止密码子的真核生物信使核糖核酸（mRNA）会经历加速周转，即所谓的无义介导的衰变（NMD）。要识别提前的翻译终止事件，需要一个监测复合体，其中包括RNA解旋酶Upf1p。在酿酒酵母中，NMD会引发快速脱帽，随后是5'→3'外切核酸酶衰变。在这里，我们报告了一种替代的、不依赖脱帽的NMD途径，该途径涉及去腺苷酸化以及随后的3'→5'外切核酸酶衰变。通过该途径的加速周转需要Upf1p，并被翻译抑制剂环己酰亚胺阻断。去腺苷酸化的mRNA的降解需要细胞质外切体复合体的Rrp4p和Ski7p成分，以及推定的RNA解旋酶Ski2p。我们得出结论，Upf监测复合体对NMD底物的识别可以将mRNA靶向快速去腺苷酸化和外切体介导的降解。
