Nonsense-mediated messenger RNA decay is initiated by endonucleolytic cleavage in Drosophila

被引:183
作者
Gatfield, D [1 ]
Izaurralde, E [1 ]
机构
[1] European Mol Biol Lab, D-69117 Heidelberg, Germany
关键词
D O I
10.1038/nature02559
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In eukaryotic cells, messenger RNAs harbouring premature termination codons (PTCs) are rapidly degraded by a conserved post-transcriptional mechanism referred to as nonsense-mediated mRNA decay (NMD)(1,2), which prevents the synthesis of truncated proteins that could be deleterious for the cell(1,2). Studies in yeast and mammals indicate that degradation by means of this pathway can occur from both the 5' end of the message (involving decapping and 5'-to-3' exonucleolytic digestion by XRN1) or the 3' end (through accelerated deadenylation and exosome-mediated 3'-to-5' decay)(3-9). Here we show that, contrary to expectation, degradation of PTC-containing messages in Drosophila is initiated by endonucleolytic cleavage(s) in the vicinity of the nonsense codon. The resulting 5' fragment is rapidly degraded by exonucleolytic digestion by the exosome, whereas the 3' fragment is degraded by XRN1. This decay route is shown for several PTC-containing reporters, as well as an endogenous mRNA that is naturally regulated by NMD. We conclude that, despite conservation in the NMD machinery, PTC-containing transcripts are degraded in Drosophila by a mechanism that differs considerably from those described in yeast and mammals(3,6,7).
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页码:575 / 578
页数:4
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