title: An NMD pathway in yeast involving accelerated deadenylation and exosome-mediated 3'-->5' degradation.
abstract: 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.
authors.affiliation: Wellcome Trust Centre for Cell Biology, Institute for Cell and Molecular Biology, King's Buildings, University of Edinburgh, EH9 3JR, United Kingdom. pmitch@holyrood.ed.ac.uk
authors.forename: Philip
authors.initials: P
authors.lastname: Mitchell
authors.forename: David
authors.initials: D
authors.lastname: Tollervey
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing; D000225:Adenine / Q000378:metabolism; D002478:Cells, Cultured; D018389:Codon, Nonsense / Q000235:genetics*; D005057:Eukaryotic Cells / Q000378:metabolism*; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics; D020365:RNA Helicases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D018389:Codon, Nonsense; D012333:RNA, Messenger; C098788:RRP4 protein, S cerevisiae; C081929:SKI2 protein, S cerevisiae; C118668:SKI7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D005095:Exoribonucleases; D019204:GTP-Binding Proteins; C074151:NAM7 protein, S cerevisiae; D020365:RNA Helicases; D000225:Adenine