An NMD pathway in yeast involving accelerated deadenylation and exosome-mediated 3′→5′ degradation
An NMD pathway in yeast involving accelerated deadenylation and exosome-mediated 3′→5′ degradation
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DOI：
10.1016/s1097-2765(03)00190-4
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发表时间：
2003-05-01
期刊：
影响因子：
16
通讯作者：
Tollervey, D
中科院分区：
文献类型：
--
作者：
Mitchell, P;Tollervey, D
含有过早终止密码子的真核mrna受到加速周转，称为无义介导的衰变（NMD）。识别翻译终止事件是否过早需要一个监视复合体，其中包括RNA解旋酶Upf1p。在酿酒酵母菌中，NMD引起快速脱帽，随后是5‘- 3’外核溶解衰变。在这里，我们报告了另一种独立于脱冠的NMD途径，涉及死基化和随后的3‘- bbb50 ’核外溶性衰变。通过这一途径加速转换需要Upf1p，并被翻译抑制剂环己亚胺阻断。死基化mRNA的降解需要胞质外胞体复合体的Rrp4p和Ski7p组分，以及假定的RNA解旋酶Ski2p。我们得出结论，Upf监视复合体对NMD底物的识别可以靶向mrna快速死蛋白化和外泌体介导的降解。
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.