Affinage

DCP2

m7GpppN-mRNA hydrolase · UniProt Q8IU60

Length
420 aa
Mass
48.4 kDa
Annotated
2026-06-09
55 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DCP2 is the catalytic subunit of the eukaryotic mRNA decapping enzyme, hydrolyzing the m7GpppN 5' cap of target mRNAs through its MutT/Nudix domain to produce m7GDP and a 5'-monophosphorylated RNA, thereby committing transcripts to 5'-to-3' degradation and serving as a central node in cytoplasmic mRNA turnover (PMID:10508173, PMID:12486012). Catalysis requires a metal ion coordinated by active-site residues that perform acid/base chemistry, with a metal-binding loop that rearranges during the catalytic cycle (PMID:23911090). Decapping is governed by a conformational equilibrium in which DCP2 samples open, closed, and catalytically active states; a conserved gatekeeper tryptophan controls the open-to-closed transition, and mRNA substrate together with the obligate partner DCP1 shifts the equilibrium toward the active conformation, in which residues from both DCP2 and DCP1 cooperate to bind RNA and raise substrate affinity (PMID:18280239, PMID:22323607, PMID:27183195, PMID:28533364). The intrinsically disordered DCP2 C-terminal extension carries both an autoinhibitory negative element and an array of positive cis-regulatory motifs—including helical leucine-rich motifs and dedicated binding sites—that recruit coactivators Edc1/Edc2, Edc3, Scd6, Pat1, and Upf1 to assemble distinct decapping complexes conferring substrate specificity toward NMD substrates and other transcript classes (PMID:21148770, PMID:22085934, PMID:26184073, PMID:29078363, PMID:35604319). In metazoans EDC4 (Hedls) acts as a scaffold that simultaneously binds DCP1, DCP2, and XRN1 to couple decapping with downstream exonucleolytic degradation, while uncomplexed DCP2 is targeted for ubiquitin-mediated proteasomal degradation (PMID:24510189, PMID:25870104). DCP2 localizes to and is required for P-bodies, and P-body enrichment is the strongest correlate of DCP2-dependent decay in human cells (PMID:16177138, PMID:22085934, PMID:32365300). Beyond bulk turnover, DCP2 substrate selection is shaped by 5'-proximal stem-loop structure and the identity of the first transcribed nucleotide, and DCP2 executes regulated decay in miRNA-mediated silencing, innate antiviral responses, oocyte maternal mRNA clearance, and restriction of LINE-1 retrotransposition (PMID:19233875, PMID:16815998, PMID:22252322, PMID:23824541, PMID:23136299, PMID:37437058). Phosphorylation of DCP2 by Ste20 during stress modulates its interactions and P-body accumulation, adding post-translational control (PMID:20513766).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1999 High

    Establishing that DCP2 is genetically required for decapping and that its Nudix motif is essential answered whether a dedicated enzyme drives cap removal in vivo.

    Evidence Genetic suppressor screen, Co-IP with Dcp1, and in vivo decay assays in yeast

    PMID:10508173

    Open questions at the time
    • Did not establish whether Dcp2 is itself the catalytic hydrolase or an essential cofactor
    • Nature of the Dcp1-Dcp2 interaction (direct vs indirect) left open
  2. 2002 High

    Reconstitution of human DCP2 as the catalytically active enzyme producing m7GDP defined DCP2 as the decapping catalyst and showed conservation and P-body localization.

    Evidence Recombinant protein, in vitro decapping assay, mutagenesis, immunofluorescence co-localization with hDcp1

    PMID:12486012

    Open questions at the time
    • Mechanism of cap recognition and the structural basis of catalysis unresolved
    • How DCP1 contributes to activity not yet defined
  3. 2005 Medium

    Loss-of-function in Drosophila placed the DCP1:DCP2 complex downstream of miRNA-directed and CCR4:NOT-coupled mRNA decay, connecting decapping to regulated silencing pathways.

    Evidence RNAi depletion, reporter mRNA stability and polysome analyses in S2 cells

    PMID:16177138 PMID:16815998

    Open questions at the time
    • Did not establish whether DCP2 acts directly on silenced transcripts or downstream of deadenylation
    • Distinction between decay and translational repression only partially separated
  4. 2005 High

    In vitro substrate studies showed DCP2 acts on diverse caps (including trimethylguanosine) and is sensitive to 5'-end sequence/structure, beginning to define substrate determinants.

    Evidence In vitro decapping with cap analogs and competing RNA across three species

    PMID:16199859

    Open questions at the time
    • Physiological relevance of TMG decapping in cells not established
    • Structural basis for 5'-context sensitivity unknown at this stage
  5. 2008 High

    Structural and NMR analyses revealed the bipartite RNA-binding channel and open/closed conformations, establishing that DCP1 stimulates catalysis by stabilizing the closed conformation rather than directly contacting the cap.

    Evidence X-ray crystallography of S. pombe Dcp1-Dcp2, SAXS, NMR, kinetics, mutagenesis

    PMID:18280238 PMID:18280239

    Open questions at the time
    • Atomic geometry of the fully active catalytic state not yet captured
    • How coactivators beyond Dcp1 reshape the equilibrium unknown
  6. 2007 Medium

    Demonstration of transcript-specific decapping (Rrp41 5' element) showed DCP2 selectivity confers regulation of individual mRNAs, not just bulk turnover.

    Evidence RNA immunoprecipitation, in vitro decapping, RNAi with mRNA stability measurement

    PMID:18039849

    Open questions at the time
    • Generality of intrinsic sequence-directed selectivity across the transcriptome not tested
    • Single lab
  7. 2009 Medium

    Identification of 5'-proximal stem-loops as enhancers of DCP2 decapping clarified that secondary structure, not primary sequence, is a key intrinsic substrate determinant.

    Evidence In vitro decapping and transfection assays with RNA secondary-structure mutants

    PMID:19233875

    Open questions at the time
    • Structural mechanism by which DCP2 recognizes stem-loops not resolved
    • Single lab
  8. 2010 High

    Defining Edc1/Edc2, Edc3, and Ste20-phosphorylation inputs established that coactivators and PTMs tune DCP2 activity, P-body recruitment, and substrate-specific decay.

    Evidence Kinetics and mutagenesis (Edc1/Edc2 via Dcp1 EVH1; 1000-fold stimulation), Edc3 peptide-binding mapping, Ste20 kinase assays and P-body microscopy in yeast

    PMID:20086104 PMID:20513766 PMID:21148770

    Open questions at the time
    • How distinct coactivators are selected for particular substrates not yet defined
    • In vivo writer/eraser dynamics of S137 phosphorylation incomplete
  9. 2011 High

    The Edc3 LSm–HLM crystal structure showed that multiple helical leucine-rich motifs in the DCP2 C-terminal extension recruit Edc3/Scd6 and are required for P-body localization, defining the C-terminal IDR as a modular activator-docking platform.

    Evidence X-ray crystallography, in vitro decapping, P-body microscopy, mutagenesis in yeast

    PMID:22085934

    Open questions at the time
    • Functional division of labor among the multiple HLMs not yet mapped
    • Competition between Edc3 and Scd6 in vivo consequences unclear at this stage
  10. 2012 High

    A conserved gatekeeper tryptophan was shown to govern conformational dynamics, mechanistically linking domain motion to coactivation by Edc1.

    Evidence NMR dynamics, kinetics, mutagenesis in S. pombe Dcp2

    PMID:22323607

    Open questions at the time
    • Quantitative populations of conformational states in the catalytic cycle not fully defined here
  11. 2012 Medium

    Cellular studies extended DCP2 function to regulated programs—innate immunity (IRF-7 mRNA stability) and viral restriction (oocyte/embryo context follows)—showing decapping shapes biological responses.

    Evidence Dcp2 hypomorphic mouse cells, mRNA stability assays, RT-PCR, immunoblot

    PMID:22252322

    Open questions at the time
    • Whether IRF-7 is a direct DCP2 substrate not definitively shown
    • Single lab
  12. 2013 High

    Catalytic-domain structures and kinetics defined the essential metal ion, active-site acid/base residues, and a mobile metal-binding loop, providing the chemical mechanism of cap hydrolysis.

    Evidence X-ray crystallography, kinetics/mutagenesis, NMR, molecular dynamics

    PMID:23911090

    Open questions at the time
    • Coupling between catalytic-domain chemistry and global conformational activation not fully integrated here
  13. 2013 Medium

    Genetic/functional studies placed DCP2 in antiviral defense against bunyaviruses and in maternal mRNA clearance during oocyte maturation, broadening its physiological repertoire.

    Evidence Genome-wide RNAi screen, RNA-seq and cap-snatching analysis in Drosophila; knockdown and kinase-inhibitor experiments in mouse oocytes

    PMID:23136299 PMID:23824541

    Open questions at the time
    • Mechanism linking decapping to suppression of viral transcription incompletely defined
    • Direct DCP2 substrates during oocyte maturation not enumerated
  14. 2016 High

    High-resolution structures of activated Dcp1-Dcp2 with Edc1, PNRC2, Edc3, and cap analog/product captured the catalytically active conformation, showing a catalytic-domain rotation that forms a composite cap/RNA-binding site and explains activation via increased substrate affinity.

    Evidence Multiple X-ray structures (1.6–2.84 Å) with kinetics and mutagenesis across fission/budding yeast

    PMID:27183195 PMID:27694841 PMID:27694842 PMID:29559651

    Open questions at the time
    • Solution populations of the active state still required orthogonal validation (addressed 2017)
    • Generalization of short-linear-motif coactivation to metazoan DCP2 not structurally shown
  15. 2017 High

    Methyl-TROSY NMR resolved three solution conformations and showed the active state forms only with both activators and substrate/product, completing the dynamic model of conformational selection.

    Evidence Methyl TROSY NMR, crystallography of Dcp1:Dcp2:Edc1:m7GDP, kinetics

    PMID:28533364

    Open questions at the time
    • How phosphorylation or scaffolds modulate this equilibrium in cells untested here
  16. 2017 High

    Defining Pat1 and Scd6 recognition of DCP2 HLMs, and Scd6/Dhh1 cooperation, clarified how distinct activators dock to the C-terminal IDR and couple translational repression with turnover.

    Evidence Crystallography of Pat1-HLM complexes; tethering, epistasis, ribosome profiling and RNA-seq for Scd6

    PMID:29078363 PMID:30532217

    Open questions at the time
    • Combinatorial logic of simultaneous activator occupancy on a single DCP2 not fully resolved
  17. 2015 Medium

    Identification of negative and positive cis-regulatory elements in the DCP2 C-terminal domain, and competition between EDC4-mediated assembly and ubiquitin-driven degradation, established autoinhibition and protein-level control of decapping.

    Evidence Genetic deletion/mutation series in yeast; ubiquitin inhibitors, Co-IP, protein-stability assays in human cells

    PMID:20104 PMID:26184073

    Open questions at the time
    • E3 ligase targeting uncomplexed DCP2 not identified
    • Single lab for each system
  18. 2018 High

    EDC4/Hedls was defined as a metazoan scaffold providing separate binding sites for DCP1, DCP2, and XRN1, physically coupling decapping to 5'-to-3' degradation.

    Evidence Reciprocal Co-IP, pull-downs, mutagenesis, reporter decay assays in human cells

    PMID:24510189

    Open questions at the time
    • Stoichiometry and structural architecture of the full EDC4-bridged assembly unresolved
  19. 2020 Medium

    Transcriptome-wide profiling and a selective chemical inhibitor defined the human DCP2 regulome, showing P-body enrichment as the strongest correlate of DCP2-dependent decay and identifying new substrates.

    Evidence TimeLapse-seq in DCP2-KO human cells; bicyclic peptide inhibitor (CP21) with cellular RNA-stability and P-body assays; Pby1 structure for P-body recruitment

    PMID:32365300 PMID:32396195 PMID:33357462

    Open questions at the time
    • Causality between P-body partitioning and decay vs correlation unresolved
    • Direct vs indirect status of many inhibitor-revealed substrates not validated
  20. 2022 Medium

    Phase-separation and IDR-interaction studies (TTP, and Upf1/NMD-substrate targeting motifs) connected DCP2 condensate behavior and C-terminal cis-elements to substrate-class-specific decay.

    Evidence Pull-downs, in vitro phase separation, mRNA stability for TTP; extensive genetic/epistasis mapping of Upf1/Edc3/Pat1/Scd6/Xrn1 motifs in yeast

    PMID:35604319 PMID:36130271

    Open questions at the time
    • In vivo requirement of phase separation for catalysis not established
    • Quantitative contribution of each motif to specificity incomplete
  21. 2023 Medium

    MOV10-directed recruitment of DCP2 to LINE-1 RNA showed DCP2 can be targeted by RNA-binding adaptors to restrict retrotransposition via decapping within phase-separated RNPs.

    Evidence Co-IP, in vitro phase separation, LINE-1 retrotransposition reporter assays with DCP2 perturbation

    PMID:37437058

    Open questions at the time
    • Direct decapping of LINE-1 RNA by DCP2 vs indirect effects not fully separated
    • Single lab
  22. 2025 Medium

    Mapping of Upf1 contacts and the Upf1/Upf2 competition at the CH domain refined how the NMD decapping complex is assembled and anchored to target mRNAs.

    Evidence Recombinant protein interaction and competition assays with purified components

    PMID:40071934

    Open questions at the time
    • Structural model of the full Upf1-anchored decapping complex not determined
    • In vivo ordering of assembly events not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DCP2 condensate/phase-separation behavior, conformational dynamics, PTMs, and combinatorial coactivator occupancy are integrated in living cells to select specific substrates remains unresolved.
  • No in-cell measurement linking conformational state to substrate choice
  • E3 ligase and full PTM code controlling DCP2 abundance unknown
  • Causal role of P-body/condensate partitioning in catalysis untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0140098 catalytic activity, acting on RNA 4 GO:0016787 hydrolase activity 3
Localization
GO:0005829 cytosol 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-168256 Immune System 2
Partners
DCP1EDC3EDC4MOV10PAT1SCD6UPF1XRN1
Complex memberships
DCP1-DCP2 decapping complexEDC4 (Hedls) decapping/XRN1 scaffold complexP-bodyUpf1-containing NMD decapping complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Yeast Dcp2 is required for mRNA decapping of both normal mRNAs and NMD substrates; its MutT/Nudix motif is necessary and sufficient for decapping function; Dcp2 co-immunoprecipitates with Dcp1 and is required for production of enzymatically active decapping enzyme, indicating direct or indirect Dcp1-Dcp2 interaction is needed for activity. Genetic suppressor screen, co-immunoprecipitation, mutational analysis, in vivo mRNA decay assays The EMBO journal High 10508173
2002 Human Dcp2 (hDcp2) is the catalytically active decapping enzyme; its MutT/Nudix domain mediates activity; it generates m7GDP and 5'-phosphorylated mRNA products; hDcp1 and hDcp2 co-localize in specific cytoplasmic foci (P-bodies); Dcp2 activity is evolutionarily conserved. Recombinant protein expression, in vitro decapping assay, mutational analysis, immunofluorescence co-localization The EMBO journal High 12486012
2005 The DCP1:DCP2 decapping complex is required for miRNA-mediated gene silencing in Drosophila cells; depletion of DCP1 or DCP2 inhibits miRNA-mediated decay of reporter mRNAs. RNAi depletion in Drosophila S2 cells, reporter assays RNA (New York, N.Y.) Medium 16177138
2005 Nematode Dcp2 decaps both m7GpppG- and m2,2,7GpppG (trimethylguanosine)-capped RNAs; Dcp2 activity is influenced by the sequence and structural context of the 5' end of the mRNA substrate; budding yeast and human Dcp2 are also active on trimethylguanosine-capped substrates; Dcp1 does not significantly enhance Dcp2 activity in nematodes. In vitro decapping assays with cap analogs, competing RNA, recombinant proteins Molecular and cellular biology High 16199859
2006 mRNA degradation by miRNAs and GW182 in Drosophila requires both the CCR4:NOT deadenylase complex and the DCP1:DCP2 decapping complex; depletion of DCP1 or DCP2 inhibits mRNA decay but not translational repression by miRNAs. RNAi depletion, reporter mRNA stability assays, polysome analysis in Drosophila S2 cells Genes & development High 16815998
2007 Human Dcp2 preferentially binds and decaps a subset of mRNAs; a 60-nucleotide element at the 5' terminus of Rrp41 mRNA serves as a specific Dcp2 substrate; reduction of hDcp2 levels selectively stabilizes Rrp41 mRNA in cells, demonstrating transcript-specific regulation. RNA immunoprecipitation, in vitro decapping assays, RNAi knockdown with mRNA stability measurement Molecular and cellular biology Medium 18039849
2008 Yeast Dcp2 uses a bipartite RNA-binding surface forming a channel that intersects the catalytic and Dcp1-binding regulatory domains; cap binding is weak but specific and requires RNA body contact; Dcp1 stimulates the catalytic step of decapping through a substrate-induced conformational change. NMR spectroscopy, enzyme kinetics Molecular cell High 18280238
2008 Crystal structure of S. pombe Dcp1-Dcp2 complex combined with SAXS reveals Dcp2 adopts open and closed conformations; the closed conformation is catalytically more active; a bipartite RNA-binding channel containing the active site is identified; Dcp1 stimulates Dcp2 activity by promoting/stabilizing the closed conformation. X-ray crystallography, SAXS, enzyme activity assays, mutagenesis Molecular cell High 18280239
2009 Enhanced decapping by Dcp2 depends on a stem-loop structure within the first 33 nucleotides of target mRNAs, not primary sequence; 5'-proximal stem-loops generally enhance Dcp2-mediated decapping; Dcp2 alone can preferentially associate with and decap stem-loop-containing substrates without additional proteins. In vitro decapping assays, mutational analysis of RNA secondary structure, transfection assays Nucleic acids research Medium 19233875
2010 Yeast Dcp2 is phosphorylated on serine 137 by the Ste20 kinase during stress; this phosphorylation affects decay of specific mRNAs, is required for Dcp2 accumulation in P-bodies, modulates specific protein interactions of Dcp2, and is required for efficient stress granule formation. In vivo phosphorylation mapping, kinase assays with Ste20, P-body fluorescence microscopy, mRNA decay assays in yeast mutants The Journal of cell biology High 20513766
2010 Edc3 binding to yeast Dcp2 is mediated by a short peptide sequence C-terminal to the catalytic domain of Dcp2; this interaction is required for Edc3 to stimulate Dcp2 decapping activity in vitro, for Dcp2 accumulation in P-bodies, and for efficient degradation of RPS28B mRNA. Mutational analysis, in vitro decapping assays, P-body fluorescence microscopy, mRNA decay assays Molecular and cellular biology High 20086104
2010 Dcp1 couples coactivator binding to Dcp2 activation; Edc1 and Edc2 bind Dcp1 via its EVH1 proline recognition site and stimulate decapping 1000-fold, affecting both substrate KM and catalytic rate; the Dcp1 EVH1 domain or Edc1 proline-rich sequence mutations block stimulation. Enzyme kinetics, mutagenesis, binding assays RNA (New York, N.Y.) High 21148770
2011 Crystal structure of yeast Edc3 LSm domain bound to a helical leucine-rich motif (HLM) from Dcp2 reveals the structural basis of interaction; multiple HLMs in the Dcp2 C-terminal extension bind Edc3; Edc3 and related Scd6 compete for the same HLMs on Dcp2; Edc3 and Scd6 stimulate decapping in vitro; C-terminal HLMs are necessary for Dcp1:Dcp2 localization to P-bodies in vivo. X-ray crystallography, in vitro decapping assays, P-body fluorescence microscopy, mutagenesis The EMBO journal High 22085934
2012 Tryptophan 43 of S. pombe Dcp2 is a conserved gatekeeper of the open-to-closed conformational transition; Dcp2 samples multiple conformations on millisecond-microsecond timescales; mutation of this tryptophan abolishes dynamic behavior and attenuates coactivation by Edc1. NMR spectroscopy, enzyme kinetics, mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 22323607
2012 Mouse Dcp2 modulates IRF-7 mRNA stability; cells with reduced Dcp2 (Dcp2β/β) show increased IRF-7 mRNA and protein due to IRF-7 mRNA stabilization; Dcp2 expression is induced upon viral infection, suggesting a negative feedback role in the innate immune response. Dcp2 hypomorphic mouse cells, mRNA stability assays, quantitative RT-PCR, immunoblot Molecular and cellular biology Medium 22252322
2013 Crystal structures of the Dcp2 catalytic Nudix domain reveal binding of a catalytically essential metal ion; active site residues involved in acid/base chemistry of decapping are identified by kinetic analysis; a conserved metal-binding loop undergoes conformational changes during the catalytic cycle as shown by NMR and molecular dynamics. X-ray crystallography, enzyme kinetics (mutagenesis), NMR, molecular dynamics simulations Structure (London, England : 1993) High 23911090
2013 Dcp2, the catalytic decapping component, and decapping activators DDX6 and LSM7 are antiviral against bunyaviruses in Drosophila; RVFV cap-snatches from Dcp2-targeted mRNAs; loss of Dcp2 increases viral transcription without affecting viral mRNA stability, while Dcp2 overexpression impedes viral transcription. Genome-wide RNAi screen, gain/loss-of-function in cells and flies, RNA-seq, cap-snatching analysis Genes & development Medium 23824541
2013 Maternally recruited DCP1A and DCP2 are translated during mouse oocyte maturation via cytoplasmic polyadenylation; both proteins are phosphorylated during maturation with CDC2A as the likely kinase; inhibition of DCP1A and DCP2 decreases maternal mRNA degradation during meiotic maturation and impairs zygotic genome activation. Immunofluorescence, morpholino/RNAi knockdown, kinase inhibitor experiments, mRNA stability assays in mouse oocytes Biology of reproduction Medium 23136299
2014 In human/metazoan cells, EDC4 acts as a scaffold that provides separate binding sites for DCP1, DCP2, and XRN1; DCP2 and XRN1 bind simultaneously to the EDC4 C-terminal domain via short linear motifs; DCP1 and DCP2 form direct but weak interactions that are facilitated by EDC4; the NR-loop in DCP1's EVH1 domain is critical for DCP2 activation; EDC4 couples DCP2 activation with XRN1-mediated 5'-to-3' degradation. Co-immunoprecipitation, pull-down assays, mutagenesis, reporter mRNA decay assays in human cells Nucleic acids research High 24510189
2015 The Dcp2 C-terminal domain contains distinct conserved negative and positive regulatory elements; a single negative element inhibits enzymatic activity and controls downstream functions; positive elements recruit decapping activators Edc3, Pat1, and Upf1 to form distinct decapping complexes controlling substrate specificity. Genetic analysis of Dcp2 C-terminal deletion/mutation series in S. cerevisiae, mRNA decay assays RNA (New York, N.Y.) Medium 26184073
2015 Human Dcp2 levels and activity are controlled by competition between decapping complex assembly and ubiquitin-mediated proteasomal degradation; the Dcp2 C-terminal regulatory domain promotes activation via Hedls (EDC4) binding on one hand, and targets uncomplexed Dcp2 for proteasomal degradation on the other. Ubiquitin pathway inhibitors, co-immunoprecipitation, protein stability assays, mutagenesis in human cells Molecular and cellular biology Medium 25870104
2016 Crystal structure (1.6 Å) of S. pombe Dcp2-Dcp1 in activated conformation stabilized by an intrinsically disordered Edc1 peptide; an unforeseen rotation of the Dcp2 catalytic domain allows residues from both Dcp2 and Dcp1 to cooperate in RNA binding; this explains decapping activation by increased substrate affinity. X-ray crystallography (1.6 Å), mutagenesis, enzyme activity assays Nature structural & molecular biology High 27183195
2016 Crystal structure (2.6 Å) of fission yeast Dcp2-Dcp1-PNRC2 heterotrimer with cap analog reveals a composite nucleotide-binding site formed by conserved residues from both Dcp2 catalytic and regulatory domains; cap binding is accompanied by a conformational change in Dcp2; PNRC2 (a short linear motif coactivator) enhances both substrate affinity and the catalytic step. X-ray crystallography (2.6 Å), enzyme kinetics, mutagenesis Nature structural & molecular biology High 27694842
2016 Crystal structure of the active form of yeast Dcp1-Dcp2 bound to the reaction product m7GDP and activator Edc3 (K. lactis); provides structural explanation for substrate binding and Edc3-mediated Dcp2 activation. X-ray crystallography, enzyme activity assays Nature structural & molecular biology High 27694841
2017 Methyl TROSY NMR demonstrates that Dcp2 in solution adopts three domain orientations (open, closed, catalytically active); mRNA substrate, Dcp1, and Edc1 shift dynamic equilibria toward the active state; the active state is only stably formed in the presence of both activators and mRNA substrate or m7GDP product; crystal structure of Dcp1:Dcp2:Edc1:m7GDP complex confirmed active state. Methyl TROSY NMR spectroscopy, X-ray crystallography, enzyme kinetics Proceedings of the National Academy of Sciences of the United States of America High 28533364
2017 Yeast Pat1 C-terminal domain interacts with multiple short HLMs (helical leucine-rich motifs) in the Dcp2 C-terminal region; crystal structures reveal the basis for HLM recognition; Pat1 also interacts with an HLM in Xrn1; Pat1 ability to bind HLMs is required for efficient growth and normal mRNA decay. X-ray crystallography of Pat1-HLM complexes, pull-down assays, mRNA decay assays, yeast genetics Proceedings of the National Academy of Sciences of the United States of America High 29078363
2018 Crystal structure (2.84 Å) of K. lactis Dcp1-Dcp2 with coactivators Edc1 and Edc3 and substrate analog in active site; Edc1 forms a three-way interface bridging Dcp2 domains to consolidate the active conformation; Dcp2 has selectivity for the first transcribed nucleotide during catalysis; Edc1 and Edc3 can simultaneously activate decapping. X-ray crystallography (2.84 Å), enzyme kinetics, mutagenesis Nature communications High 29559651
2018 Yeast Scd6 activates Dcp2-mediated mRNA decapping and mRNA turnover through its LSm domain in vivo; in a dcp2Δ mutant, tethered Scd6 represses translation without reducing mRNA abundance; in a dcp2Δ dhh1Δ double mutant, Scd6 has no impact on mRNA or protein levels; Scd6 and Dhh1 cooperate in translational repression and mRNA turnover of specific native mRNAs. Tethering assay, genetic epistasis (dcp2Δ, dhh1Δ), ribosome profiling, RNA-Seq PLoS genetics High 30532217
2020 Yeast Pby1 directly binds the Dcp1-Dcp2 decapping complex through its C-terminal domain; crystal structure of Pby1-C-terminal domain bound to Dcp1-Dcp2-Edc3 complex is solved; Pby1 binding requires direct interaction with the decapping enzyme for P-body recruitment; Pby1 binding stimulates growth under conditions of compromised decapping activation. X-ray crystallography, pull-down assays, P-body fluorescence microscopy, yeast growth assays, mutagenesis Nucleic acids research High 32396195
2020 P-body enrichment is the strongest correlate of Dcp2-dependent decay in human cells; m6A modification has an additive effect with P-body enrichment for Dcp2 targeting; global profiling in Dcp2 knockout cells via TimeLapse-seq identified the human Dcp2 regulome. TimeLapse-seq in Dcp2 knockout human cells, bioinformatic correlation analysis Biochemistry Medium 32365300
2020 A bicyclic peptide inhibitor (CP21) selectively binds human DCP2 and inhibits its decapping activity toward selected RNA substrates in human cells; DCP2 inhibition increases P-body formation similar to DCP2 deletion; CP21 enabled identification of 76 previously unreported DCP2 substrates. Phage display selection, biochemical binding assays, cell-based RNA stability assays, P-body fluorescence microscopy Cell chemical biology Medium 33357462
2022 Yeast Dcp2 C-terminal domain cis-regulatory elements control decapping target specificity: two Upf1-binding motifs direct the enzyme to NMD substrates; a single Edc3-binding motif targets Edc3 and Dhh1 substrates; Pat1-binding leucine-rich motifs target Edc3/Dhh1 substrates under selective conditions; Scd6 and Xrn1 also have specific binding sites on Dcp2. Extensive genetic and mutational analysis in S. cerevisiae, mRNA decay assays, epistasis analysis eLife High 35604319
2022 Human DCP2 and tristetraprolin (TTP) interact directly via their intrinsically disordered regions (IDRs); this interaction impacts ARE-mRNA stability; the DCP2 IDR has a propensity for oligomerization and liquid-liquid phase separation in vitro; TTP partitions into DCP2 phase-separated droplets, suggesting molecular crowding facilitates assembly of a decapping-competent complex. Pull-down assays, in vitro phase separation assays, mass spectrometry (Urlaub), mRNA stability assays Nucleic acids research Medium 36130271
2023 MOV10 recruits DCP2 to LINE-1 RNA, forming a MOV10-DCP2-LINE-1 RNP complex with liquid-liquid phase separation properties; DCP2 cooperates with MOV10 to decap LINE-1 RNA, causing LINE-1 RNA degradation and reducing retrotransposition. Co-immunoprecipitation, in vitro phase separation assays, LINE-1 retrotransposition reporter assays, DCP2 overexpression/knockdown EMBO reports Medium 37437058
2008 SSA/Ro52 autoantigen binds human DCP2 at both its N- and C-termini and co-localizes with DCP2 in P-bodies; Ro52 enhances DCP2 decapping activity in a dose-dependent manner. Co-immunoprecipitation, in vitro decapping assay, immunofluorescence co-localization Biochemical and biophysical research communications Low 18361920
2025 Distinct domains of yeast Upf1 make direct contacts with Dcp1/Dcp2, Nmd4, and Ebs1 in the NMD decapping complex; Dcp2 and Upf2 compete for the same binding site on the N-terminal CH domain of Upf1, explaining two mutually exclusive Upf1-containing complexes; Nmd4-assisted recruitment of Upf1 promotes anchoring of the decapping enzyme to NMD target mRNAs. Recombinant protein interaction assays, pull-down with purified components, competition assays Nucleic acids research Medium 40071934
2025 In vitro, eIF4E does not interfere with DCP2 decapping function (negative result contradicting prior models); eIF4E binding increases the affinity of Dcp2 for RNA; DCP2 binds RNA with nanomolar affinity as measured by biophysical assays. Purified recombinant proteins, biophysical binding assays, in vitro decapping assays PloS one Low 40748882

Source papers

Stage 0 corpus · 55 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes. Genes & development 737 16815998
2002 Human Dcp2: a catalytically active mRNA decapping enzyme located in specific cytoplasmic structures. The EMBO journal 400 12486012
2005 A crucial role for GW182 and the DCP1:DCP2 decapping complex in miRNA-mediated gene silencing. RNA (New York, N.Y.) 368 16177138
1999 The DCP2 protein is required for mRNA decapping in Saccharomyces cerevisiae and contains a functional MutT motif. The EMBO journal 284 10508173
2008 Structural basis of dcp2 recognition and activation by dcp1. Molecular cell 116 18280239
2014 The activation of the decapping enzyme DCP2 by DCP1 occurs on the EDC4 scaffold and involves a conserved loop in DCP1. Nucleic acids research 102 24510189
2011 The structural basis of Edc3- and Scd6-mediated activation of the Dcp1:Dcp2 mRNA decapping complex. The EMBO journal 101 22085934
2008 mRNA decapping is promoted by an RNA-binding channel in Dcp2. Molecular cell 86 18280238
2013 A genome-wide RNAi screen reveals that mRNA decapping restricts bunyaviral replication by limiting the pools of Dcp2-accessible targets for cap-snatching. Genes & development 82 23824541
2010 Dcp2 phosphorylation by Ste20 modulates stress granule assembly and mRNA decay in Saccharomyces cerevisiae. The Journal of cell biology 81 20513766
2013 Maternally recruited DCP1A and DCP2 contribute to messenger RNA degradation during oocyte maturation and genome activation in mouse. Biology of reproduction 66 23136299
2005 Caenorhabditis elegans decapping proteins: localization and functional analysis of Dcp1, Dcp2, and DcpS during embryogenesis. Molecular biology of the cell 57 16207815
2007 Transcript-specific decapping and regulated stability by the human Dcp2 decapping protein. Molecular and cellular biology 55 18039849
2010 Identification and analysis of the interaction between Edc3 and Dcp2 in Saccharomyces cerevisiae. Molecular and cellular biology 49 20086104
2015 Control of mRNA decapping by positive and negative regulatory elements in the Dcp2 C-terminal domain. RNA (New York, N.Y.) 46 26184073
2016 Structure of the Dcp2-Dcp1 mRNA-decapping complex in the activated conformation. Nature structural & molecular biology 45 27183195
2010 Dcp1 links coactivators of mRNA decapping to Dcp2 by proline recognition. RNA (New York, N.Y.) 45 21148770
2016 Structural basis of mRNA-cap recognition by Dcp1-Dcp2. Nature structural & molecular biology 44 27694842
2017 A unique surface on Pat1 C-terminal domain directly interacts with Dcp2 decapping enzyme and Xrn1 5'-3' mRNA exonuclease in yeast. Proceedings of the National Academy of Sciences of the United States of America 42 29078363
2016 Structure of the active form of Dcp1-Dcp2 decapping enzyme bound to m7GDP and its Edc3 activator. Nature structural & molecular biology 42 27694841
2005 Dcp2 Decaps m2,2,7GpppN-capped RNAs, and its activity is sequence and context dependent. Molecular and cellular biology 42 16199859
2017 Changes in conformational equilibria regulate the activity of the Dcp2 decapping enzyme. Proceedings of the National Academy of Sciences of the United States of America 39 28533364
2018 Structure of the activated Edc1-Dcp1-Dcp2-Edc3 mRNA decapping complex with substrate analog poised for catalysis. Nature communications 36 29559651
2012 Dcp2 decapping protein modulates mRNA stability of the critical interferon regulatory factor (IRF) IRF-7. Molecular and cellular biology 35 22252322
2019 Dcp2: an mRNA decapping enzyme that adopts many different shapes and forms. Current opinion in structural biology 32 31473440
2018 Conserved mRNA-granule component Scd6 targets Dhh1 to repress translation initiation and activates Dcp2-mediated mRNA decay in vivo. PLoS genetics 32 30532217
2012 Interdomain dynamics and coactivation of the mRNA decapping enzyme Dcp2 are mediated by a gatekeeper tryptophan. Proceedings of the National Academy of Sciences of the United States of America 30 22323607
2020 Global Profiling of Cellular Substrates of Human Dcp2. Biochemistry 27 32365300
2009 Mutational analysis of a Dcp2-binding element reveals general enhancement of decapping by 5'-end stem-loop structures. Nucleic acids research 25 19233875
2015 Competition between Decapping Complex Formation and Ubiquitin-Mediated Proteasomal Degradation Controls Human Dcp2 Decapping Activity. Molecular and cellular biology 22 25870104
2013 Active site conformational dynamics are coupled to catalysis in the mRNA decapping enzyme Dcp2. Structure (London, England : 1993) 22 23911090
2022 Dcp2 C-terminal cis-binding elements control selective targeting of the decapping enzyme by forming distinct decapping complexes. eLife 18 35604319
2020 Discovery of cellular substrates of human RNA-decapping enzyme DCP2 using a stapled bicyclic peptide inhibitor. Cell chemical biology 15 33357462
2023 Decapping factor Dcp2 controls mRNA abundance and translation to adjust metabolism and filamentation to nutrient availability. eLife 12 37266577
2023 MOV10 recruits DCP2 to decap human LINE-1 RNA by forming large cytoplasmic granules with phase separation properties. EMBO reports 11 37437058
2008 Control of mRNA decapping by Dcp2: An open and shut case? RNA biology 11 18971632
2017 Application of a Schizosaccharomyces pombe Edc1-fused Dcp1-Dcp2 decapping enzyme for transcription start site mapping. RNA (New York, N.Y.) 10 29101277
2022 Intrinsically disordered regions of tristetraprolin and DCP2 directly interact to mediate decay of ARE-mRNA. Nucleic acids research 9 36130271
2017 Pervasive yet nonuniform contributions of Dcp2 and Cnot7 to maternal mRNA clearance in zebrafish. Genes to cells : devoted to molecular & cellular mechanisms 9 28557307
2015 Tob1 is expressed in developing and adult gonads and is associated with the P-body marker, Dcp2. Cell and tissue research 9 26662055
2020 Global deletion of the RNA decapping enzyme Dcp2 postnatally in male mice results in infertility. Biochemical and biophysical research communications 7 32245620
2008 SSA/Ro52 autoantigen interacts with Dcp2 to enhance its decapping activity. Biochemical and biophysical research communications 6 18361920
2020 Pby1 is a direct partner of the Dcp2 decapping enzyme. Nucleic acids research 4 32396195
2018 MicroRNA-141-3p/200a-3p target and may be involved in post-transcriptional repression of RNA decapping enzyme Dcp2 during renal development. Bioscience, biotechnology, and biochemistry 4 29912646
2025 RNA anchoring of Upf1 facilitates recruitment of Dcp2 in the NMD decapping complex. Nucleic acids research 3 40071934
2019 Role of DCP1-DCP2 complex regulated by viral and host microRNAs in DNA virus infection. Fish & shellfish immunology 3 31146005
2021 The mRNA decapping protein 2 (DCP2) is a major regulator of developmental events in Drosophila-insights from expression paradigms. Cell and tissue research 2 34536141
2020 A Forward Genetic Approach to Mapping a P-Element Second Site Mutation Identifies DCP2 as a Novel Tumor Suppressor in Drosophila melanogaster. G3 (Bethesda, Md.) 2 32591349
2023 Decapping factor Dcp2 controls mRNA abundance and translation to adjust metabolism and filamentation to nutrient availability. bioRxiv : the preprint server for biology 1 36711592
2023 Disruption of Dcp1 leads to a Dcp2-dependent aberrant ribosome profiles in Aspergillus nidulans. Molecular microbiology 1 37024243
2023 Mechanism of Dcp2/RNCR3/Dkc1/Snora62 axis regulating neuronal apoptosis in chronic cerebral ischemia. Cell biology and toxicology 1 37097350
2016 PDZ Binding Domains, Structural Disorder and Phosphorylation: A Menage-a-trois Tailing Dcp2 mRNA Decapping Enzymes. Protein and peptide letters 1 27151193
2007 Backbone and sidechain methyl Ile (delta1), Leu and Val resonance assignments of the catalytic domain of the yeast mRNA decapping enzyme, Dcp2. Biomolecular NMR assignments 1 19636815
2025 Biochemical analysis of human eIF4E-DCP2 interaction: Implications for the relationship between translation initiation and decapping. PloS one 0 40748882
2025 Developmental delay in DCP2l(3)tb of Drosophila melanogaster is due to disruption in the regulation of ecdysone signaling. Experimental cell research 0 41135857

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