Alternative titles; symbols
HGNC Approved Gene Symbol: DCP2
Cytogenetic location: 5q22.2 Genomic coordinates (GRCh38): 5:112,976,798-113,022,195 (from NCBI)
DCP2 is a key component of an mRNA-decapping complex required for removal of the 5-prime cap from mRNA prior to its degradation from the 5-prime end (Fenger-Gron et al., 2005).
By searching for genes similar to S. cerevisiae Dcp2, Lykke-Andersen (2002) identified human DCP2, which encodes a deduced 420-amino acid protein. Epitope-tagged DCP2 localized to punctate cytoplasmic foci, with some nuclear staining.
By searching for sequences similar to the 23-amino acid Nudix motif of yeast Dcp2, followed by RT-PCR of a K562 erythroleukemia cell line cDNA library, Wang et al. (2002) cloned human DCP2. The deduced protein contains 3 conserved regions: the 109-amino acid Nudix fold and its flanking A and B boxes. The Nudix motif within the fold contains 2 glutamic acids (glu147 and glu148) critical for metal ion coordination and pyrophosphatase activity. Western blot analysis detected endogenous DCP2 at an apparent molecular mass of 45 kD in cytoplasmic fractions of K562 cells. DCP2 predominantly cosedimented with polysomes.
Lykke-Andersen (2002) found that DCP1A (607010) and DCP2 interacted directly in an mRNA-decapping complex in an RNA-independent manner. Recombinant DCP2 expressed in E. coli and epitope-tagged DCP2 expressed by human embryonic kidney cells showed mRNA-decapping activity. Mutation of glu148 of DCP2 reduced decapping activity by 20-fold. Coimmunoprecipitation assays demonstrated that DCP1A and DCP2 interacted with the nonsense-mediated decay factor UPF1 (RENT1; 601430) both in the presence and in the absence of other UPF proteins. Lykke-Andersen (2002) concluded that UPF proteins may recruit a human decapping complex to mRNAs containing premature termination codons.
Wang et al. (2002) found that DCP2 specifically hydrolyzed methylated capped synthetic RNA to release m7GDP, but it did not hydrolyze cap analogs in the absence of the synthetic RNA sequence. Mutation of glu147 or glu148 disrupted decapping activity, indicating that decapping requires a functional Nudix pyrophosphatase motif. The presence of a poly(A) tail was inhibitory to the endogenous decapping activity.
Van Dijk et al. (2002) found that recombinant human DCP2 generated m7GDP and 5-prime-phosphorylated mRNAs. The MutT/Nudix domain was required for decapping activity.
Using mass spectroscopy, Fenger-Gron et al. (2005) found that DCP1A and DCP2 coimmunopurified with EDC3 (YJDC; 609842), RCK (DDX6; 600326), and HEDLS (RCD8; 606030) from HEK293 cell lysates. HEDLS promoted association of DCP1A and DCP2, and overexpressed DCP1A and DCP2 did not associate in its absence. HEDLS associated with DCP2 and stimulated its decapping activity in vitro. Overexpression of DCP2, RCK, or EDC3 in HeLa cells reduced the association of endogenous DCP1A and XRN1 (607994) with cytoplasmic processing bodies.
Jiao et al. (2006) found that VCXA (300533) functioned as an inhibitor of the decapping enzyme DCP2 in vitro and in human cell lines, and that it stabilized mRNA. They showed that VCXA is a noncanonical cap-binding protein that binds to capped RNA but not cap structure lacking an RNA. The association of VCXA with the cap structure was enhanced by DCP2, which augmented the ability of VCXA to inhibit decapping.
Mauer et al. (2017) showed that modification of the first encoded nucleotide adjacent to the 7-methylguanosine cap, N6,2-prime-O-dimethyladenosine (m6Am), is a reversible modification that influences cellular mRNA fate. Using a transcriptomewide map of m6Am, Mauer et al. (2017) found that m6Am-initiated transcripts are markedly more stable than mRNAs that begin with other nucleotides and showed that the enhanced stability of m6Am-initiated transcripts is due to resistance to the mRNA-decapping enzyme DCP2. Moreover, Mauer et al. (2017) found that m6Am is selectively demethylated by fat mass- and obesity-associated protein (FTO; 610966). FTO preferentially demethylates m6Am rather than N6-methyladenosine (m6A), and reduces the stability of m6Am mRNAs. Mauer et al. (2017) concluded that the methylation status of m6Am in the 5-prime cap is a dynamic and reversible epitranscriptomic modification that determines mRNA stability.
Ueno et al. (1998) identified the DCP2 gene within a contig spanning chromosome 5q21-q22. By genomic sequence analysis, Wang et al. (2002) mapped the DCP2 gene to chromosome 5q22-q23.
Fenger-Gron, M., Fillman, C., Norrild, B., Lykke-Andersen, J. Multiple processing body factors and the ARE binding protein TTP activate mRNA decapping. Molec. Cell 20: 905-915, 2005. [PubMed: 16364915] [Full Text: https://doi.org/10.1016/j.molcel.2005.10.031]
Jiao, X., Wang, Z., Kiledjian, M. Identification of an mRNA-decapping regulator implicated in X-linked mental retardation. Molec. Cell 24: 713-722, 2006. [PubMed: 17157254] [Full Text: https://doi.org/10.1016/j.molcel.2006.10.013]
Lykke-Andersen, J. Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay. Molec. Cell. Biol. 22: 8114-8121, 2002. [PubMed: 12417715] [Full Text: https://doi.org/10.1128/MCB.22.23.8114-8121.2002]
Mauer, J., Luo, X., Blanjoie, A., Jiao, X., Grozhik, A. V., Patil, D. P., Linder, B., Pickering, B. F., Vasseur, J.-J., Chen, Q., Gross, S. S., Elemento, O., Debart, F., Kiledjian, M., Jaffrey, S. R. Reversible methylation of m6Am in the 5-prime cap controls mRNA stability. Nature 541: 371-375, 2017. [PubMed: 28002401] [Full Text: https://doi.org/10.1038/nature21022]
Ueno, K., Kumagai, T., Kijima, T., Kishimoto, T., Hosoe, S. Cloning and tissue expression of cDNAs from chromosome 5q21-22 which is frequently deleted in advanced lung cancer. Hum. Genet. 102: 63-68, 1998. [PubMed: 9490301] [Full Text: https://doi.org/10.1007/s004390050655]
van Dijk, E., Cougot, N., Meyer, S., Babajko, S., Wahle, E., Seraphin, B. Human Dcp2: a catalytically active mRNA decapping enzyme located in specific cytoplasmic structures. EMBO J. 21: 6915-6924, 2002. [PubMed: 12486012] [Full Text: https://doi.org/10.1093/emboj/cdf678]
Wang, Z., Jiao, X., Carr-Schmid, A., Kiledjian, M. The hDcp2 protein is a mammalian mRNA decapping enzyme. Proc. Nat. Acad. Sci. 99: 12663-12668, 2002. [PubMed: 12218187] [Full Text: https://doi.org/10.1073/pnas.192445599]