Dcp2 is the catalytic component of the decapping complex necessary for the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay [, ]. Dcp2 contains an all-alpha N-terminal helical domain and a domain which has the Nudix fold. It has been shown that the Nudix domain of both Saccharomyces cerevisiae and S. pombe Dcp2 proteins is sufficient for decapping activity. While decapping is not dependent on the N-terminal of Dcp2, it does affect its efficiency. Dcp1 binds the N-terminal domain of Dcp2 stimulating the decapping activity of Dcp2 [].This entry represents the NUDIX hydrolase domain found in Dcp2. This domain catalyses the mRNA decapping reaction [].
This superfamily represents the highly conserved C-terminal region of Enhancer of mRNA-decapping protein 4 (EDC4, also known as Ge-1) which adopts an all α-helical fold [, ]. This domain is necessary and sufficient for P-body targeting and, in plants, it also mediates DCP1 and DCP2 interaction, as well as self-association [].
This superfamily represents the N-terminal domain of scavenger mRNA decapping enzymes, such as Dcp2 and DcpS. DcpS is a scavenger pyrophosphatase that hydrolyses the residual cap structure following 3' to 5' mRNA degradation. DcpS uses cap dinucleotides or capped oligonucleotides as substrate to release m(7)GMP (N7-methyl GMP), while Dcp2 uses capped mRNA as substrate in order to hydrolyse the cap to release m(7)GDP (N7-methyl GDP) []. The association of DcpS with 3' to 5' exonuclease exosome components suggests that these two activities are linked and there is a coupled exonucleolytic decay-dependent decapping pathway. DcpS exists as a dimer and each monomer is comprised of an N-terminal and a C-terminal region. The two N-termini form into a domain-swapped dimer and carry out substrate binding, cap dinucleotide, and hydrolysis [].
This entry represents scavenger mRNA decapping enzymes, such as Dcp2 and DcpS. DcpS is a scavenger pyrophosphatase that hydrolyses the residual cap structure following 3' to 5' mRNA degradation. DcpS uses cap dinucleotides or capped oligonucleotides as substrate to release m(7)GMP (N7-methyl GMP), while Dcp2 uses capped mRNA as substrate in order to hydrolyse the cap to release m(7)GDP (N7-methyl GDP) []. The association of DcpS with 3' to 5' exonuclease exosome components suggests that these two activities are linked and there is a coupled exonucleolytic decay-dependent decapping pathway. The family contains a histidine triad (HIT) sequence with three histidines separated by hydrophobic residues []. The central histidine within the DcpS HIT motif is critical for decapping activityand defines the HIT motif as a new mRNA decapping domain, making DcpS the first member of the HIT family of proteins with a defined biological function. This family is related to ().
This domain is found in the 5'-3' exonuclease (XRN1) present in Drosophila melanogaster. XRN1 degrades deadenylated mRNA that has recently been decapped by decapping enzyme 2 (DCP2). DCP2 associates with decapping activators DCP1 and EDC4. The direct interaction between DCP1 and XRN1 couples mRNA decapping to 5' exonucleolytic degradation. This domain is responsible for binding to DCP1. In particular, the helical C-terminal region of the domain contributes to the binding affinity and the specificity of the interaction [].
An essential step in mRNA turnover is decapping. In yeast, two proteins have been identified that are essential for decapping, Dcp1 (this family) and Dcp2. Dcp1 is a coactivator that binds to the decapping enzyme Dcp2 and forms a decapping enzyme complex, which removes the 5' cap structure from mRNAs prior to their degradation []. Yeast Dcp1 interact directly with Dcp2, however, the Dcp1-Dcp2 interaction is promoted by an additional factor, EDC4 []. In the nervous system, it promotes neurons' lifespan through the negative regulation of the insulin-like peptide ins-7 expression [].
