van Dijk Erwin, Cougot Nicolas, Meyer Sylke, Babajko Sylvie, Wahle Elmar, Séraphin Bertrand
Equipe labelisée La Ligue, Centre de Génétique Moléculaire, CNRS, Avenue de la Terrasse, 91198 Gif sur Yvette, France.
EMBO J. 2002 Dec 16;21(24):6915-24. doi: 10.1093/emboj/cdf678.
We have cloned cDNAs for the human homologues of the yeast Dcp1 and Dcp2 factors involved in the major (5'-3') and NMD mRNA decay pathways. While yeast Dcp1 has been reported to be the decapping enzyme, we show that recombinant human Dcp2 (hDcp2) is enzymatically active. Dcp2 activity appears evolutionarily conserved. Mutational and biochemical analyses indicate that the hDcp2 MutT/Nudix domain mediates this activity. hDcp2 generates m7GDP and 5'-phosphorylated mRNAs that are 5'-3' exonuclease substrates. Corresponding decay intermediates are present in human cells showing the relevance of this activity. hDcp1 and hDcp2 co-localize in cell cytoplasm, consistent with a role in mRNA decay. Interestingly, these two proteins show a non-uniform distribution, accumulating in specific foci.
我们已经克隆出了参与主要（5'-3'）和NMD mRNA降解途径的酵母Dcp1和Dcp2因子的人类同源物的cDNA。虽然据报道酵母Dcp1是去帽酶，但我们发现重组人Dcp2（hDcp2）具有酶活性。Dcp2活性在进化上似乎是保守的。突变和生化分析表明，hDcp2的MutT/Nudix结构域介导了这种活性。hDcp2产生m7GDP和5'-磷酸化的mRNA，它们是5'-3'核酸外切酶的底物。相应的降解中间体存在于人类细胞中，表明了这种活性的相关性。hDcp1和hDcp2共定位于细胞质中，这与它们在mRNA降解中的作用一致。有趣的是，这两种蛋白质显示出不均匀的分布，聚集在特定的位点。
