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Human Dcp2: a catalytically active mRNA decapping enzyme located in specific cytoplasmic structures.

Erwin van Dijk·Nicolas Cougot·Sylke Meyer·Sylvie Babajko·Elmar Wahle·Bertrand Séraphin
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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.

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Amino Acid MotifsAmino Acid SequenceBlotting, WesternCatalysisCell LineCell NucleusCloning, MolecularCytoplasmDNA, ComplementaryEndopeptidasesEndoribonucleasesGlutathione TransferaseGreen Fluorescent ProteinsHumansLuminescent ProteinsMicroscopy, FluorescenceMolecular Sequence DataPhosphorylationPlasmidsProtein Structure, TertiaryRNA, MessengerRecombinant Fusion ProteinsRecombinant ProteinsSequence Homology, Amino AcidTransfectionJournal ArticleResearch Support, Non-U.S. Gov't

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Erwin van Dijk, Nicolas Cougot, Sylke Meyer, Sylvie Babajko, Elmar Wahle, Bertrand Séraphin. 2002-12-16. Human Dcp2: a catalytically active mRNA decapping enzyme located in specific cytoplasmic structures.. https://doi.org/10.1093/emboj%2Fcdf678

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