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DECAPPING mRNA 1A; DCP1A

DECAPPING mRNA 1A; DCP1A

Alternative titles; symbolsDECAPPING ENZYME 1, S. CEREVISIAE, HOMOLOG OF, ADCP1, S. CEREVISIAE, HOMOLOG OF, ASMAD4-INTERACTING TRANSCRIPTION FACTOR; SMIFHGNC App...

Alternative titles; symbols

  • DECAPPING ENZYME 1, S. CEREVISIAE, HOMOLOG OF, A
  • DCP1, S. CEREVISIAE, HOMOLOG OF, A
  • SMAD4-INTERACTING TRANSCRIPTION FACTOR; SMIF

HGNC Approved Gene Symbol: DCP1A

Cytogenetic location: 3p21.1 Genomic coordinates (GRCh38): 3:53,283,428-53,347,542 (from NCBI)

▼ Description
DCP1A is a core component of an mRNA-decapping complex, a key factor in the regulation of mRNA decay (Lykke-Andersen, 2002). DCP1A is also a transactivator of SMAD4 (600993) and participates in the TGF-beta (190180) signaling pathway (Bai et al., 2002).

▼ Cloning and Expression
With SMAD4 as bait in a yeast 2-hybrid screen of a human pancreatic cDNA library, Bai et al. (2002) cloned DCP1A, which they called SMIF. The deduced protein contains 582 amino acids. Northern blot analysis detected a 7-kb transcript in all tissues examined. Western blot analysis revealed a 70-kD protein in several mammalian cell lines. Bai et al. (2002) also cloned mouse Smif from a 17-day embryonic cDNA library. The human and mouse proteins share 90% overall sequence identity and 98% identity in the N-terminal Smad4-binding region.

By searching for genes similar to S. cerevisiae Dcp1, Lykke-Andersen (2002) identified 2 distant human homologs, DCP1A and DCP1B (609843). Epitope-tagged DCP1A localized to punctate cytoplasmic foci, with some nuclear staining.

▼ Gene Function
Bai et al. (2002) found that SMIF interacts specifically with SMAD4 and not with any other SMAD proteins. By deletion analysis, they determined that the N-terminal 100 amino acids of SMIF and residues tyr/phe301 and trp302 of SMAD4 are required for this interaction. Cotransfection experiments demonstrated that treatment with TGF-beta or bone morphogenic protein-4 (BMP4; 112262) resulted in SMAD4/SMIF interaction, followed by their nuclear translocation and accumulation. SMIF remained cytosolic in the absence of SMAD4. With use of several transient reporter assays to monitor TGF-beta-dependent transcriptional activity, Bai et al. (2002) determined that the SMAD4/SMIF complex was the transcriptional unit, since neither protein alone was active. With use of deletion mutations, they found that the transactivation domain of SMIF is separate from the N-terminal SMAD4-binding domain and localizes to amino acids 124-390.

Lykke-Andersen (2002) found that DCP1A and DCP2 (609844) interacted directly in an mRNA-decapping complex in an RNA-independent manner. Recombinant DCP1A fused to an N-terminal GST tag was inactive in decapping activity, but FLAG-tagged DCP1A expressed in human embryonic kidney cells was active. Mutation of asn20 and arg59 reduced DCP1A decapping activity by 4- and 12-fold, respectively, and both mutations resulted in reduced protein stability. 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.

Using mass spectroscopy, Fenger-Gron et al. (2005) found that EDC3 (YJDC; 609842), RCK (DDX6; 600326), and HEDLS (RCD8; 606030) coimmunopurified with DCP1A and DCP2 (609844) from HEK293 cell lysates. Overexpression of DCP2, RCK, or EDC3 in HeLa cells reduced the association of endogenous DCP1A and XRN1 (607994) with cytoplasmic processing bodies. HEDLS was required for the interaction of overexpressed DCP1A and DCP2.

▼ Mapping
The International Radiation Hybrid Mapping Consortium mapped the SMIF gene to chromosome 3 (SGC34070).

Tags: 3p21.1