人类Dcp2：一种位于特定细胞质结构中的具有催化活性的mRNA脱帽酶。
Human Dcp2: a catalytically active mRNA decapping enzyme located in specific cytoplasmic structures.
作者信息
van Dijk Erwin, Cougot Nicolas, Meyer Sylke, Babajko Sylvie, Wahle Elmar, Séraphin Bertrand
机构信息
Equipe labelisée La Ligue, Centre de Génétique Moléculaire, CNRS, Avenue de la Terrasse, 91198 Gif sur Yvette, France.
出版信息
EMBO J. 2002 Dec 16;21(24):6915-24. doi: 10.1093/emboj/cdf678.
Abstract
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.
摘要
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。
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本文引用的文献
1
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Mol Cell. 2002 Oct;10(4):93-104.
2
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EMBO J. 2002 Jun 3;21(11):2788-97. doi: 10.1093/emboj/21.11.2788.
3
Messenger RNA degradation: beginning at the end.信使核糖核酸降解：从末端开始
Curr Biol. 2002 Apr 16;12(8):R285-7. doi: 10.1016/s0960-9822(02)00802-3.
4
A phosphorylated cytoplasmic autoantigen, GW182, associates with a unique population of human mRNAs within novel cytoplasmic speckles.一种磷酸化的细胞质自身抗原GW182，在新的细胞质斑点中与一类独特的人类mRNA相关联。
Mol Biol Cell. 2002 Apr;13(4):1338-51. doi: 10.1091/mbc.01-11-0544.
5
Exosome-mediated recognition and degradation of mRNAs lacking a termination codon.外泌体介导的对缺乏终止密码子的mRNA的识别与降解。
Science. 2002 Mar 22;295(5563):2262-4. doi: 10.1126/science.1067272.
6
An mRNA surveillance mechanism that eliminates transcripts lacking termination codons.一种消除缺乏终止密码子转录本的信使核糖核酸监测机制。
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7
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