An NMD pathway in yeast involving accelerated deadenylation and exosome-mediated 3′→5′ degradation

被引:161
作者
Mitchell, P [1 ]
Tollervey, D [1 ]
机构
[1] Univ Edinburgh, Inst Cell & Mol Biol, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland
基金
英国惠康基金;
关键词
D O I
10.1016/S1097-2765(03)00190-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1405 / 1413
页数:9
相关论文
共 50 条
  • [41] Function of the Ski4p (Csl4p) and Ski7p proteins in 3′-to-5′ degradation of mRNA
    van Hoof, A
    Staples, RR
    Baker, RE
    Parker, R
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (21) : 8230 - 8243
  • [42] Exosome-mediated recognition and degradation of mRNAs lacking a termination codon
    van Hoof, A
    Frischmeyer, PA
    Dietz, HC
    Parker, R
    [J]. SCIENCE, 2002, 295 (5563) : 2262 - 2264
  • [43] VARY CPH, 1984, J BIOL CHEM, V259, P3299
  • [44] Functional link between the mammalian exosome and mRNA decapping
    Wang, ZR
    Kiledjian, M
    [J]. CELL, 2001, 107 (06) : 751 - 762
  • [45] An internal open reading frame triggers nonsense-mediated decay of the yeast SPT10 mRNA
    Welch, EM
    Jacobson, A
    [J]. EMBO JOURNAL, 1999, 18 (21) : 6134 - 6145
  • [46] Wilusz CJ, 2001, GENE DEV, V15, P2781
  • [47] At least one intron is required for the nonsense-mediated decay of triosephosphate isomerase mRNA: a possible link between nuclear splicing and cytoplasmic translation
    Zhang, J
    Sun, XL
    Qian, YM
    LaDuca, JP
    Maquat, LE
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (09) : 5272 - 5283
  • [48] Intron function in the nonsense-mediated decay of β-globin mRNA:: Indications that pre-mRNA splicing in the nucleus can influence mRNA translation in the cytoplasm
    Zhang, J
    Sun, XL
    Qian, YM
    Maquat, LE
    [J]. RNA, 1998, 4 (07) : 801 - 815
  • [49] Zhang SA, 1997, RNA, V3, P234
  • [50] ZHANG SA, 1995, MOL CELL BIOL, V15, P2231