Affinage

DICER1

Endoribonuclease Dicer · UniProt Q9UPY3

Length
1922 aa
Mass
218.7 kDa
Annotated
2026-06-09
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DICER1 is a multidomain RNase III endoribonuclease that constitutes the central nuclease of the microRNA and small-RNA biogenesis pathway, converting double-stranded RNA and pre-miRNA hairpins into ~21-23 nt products in a Mg2+-dependent, ATP-independent reaction (PMID:12411504, PMID:15066283). Substrate length and cleavage position are set by an integrated 'molecular ruler': the PAZ domain recognizes the dsRNA end and dictates product length (PMID:17873886), a basic '5' pocket' anchors the 5'-phosphorylated end so that cleavage occurs a fixed ~22 nt distance away ('5' counting rule') (PMID:21753850), and a conserved cis-acting 'GYM motif' read by the C-terminal dsRBD positions cleavage and can override the counting rules (PMID:36813957); substrate features such as a position-22 bulge further tune accuracy (PMID:35440644). The DExD/H helicase domain performs a structural rather than catalytic role, locking the enzyme in a closed, high-selectivity conformation whose transition to a cleavage-competent open state is stimulated by the cofactor TARBP2, with cryo-EM capturing these conformational states for both mammalian Dicer and the Drosophila Dicer-1/Loqs-PB heterodimer across a full reaction cycle (PMID:23624860, PMID:36332606, PMID:36182693). DICER discriminates strongly in favor of pre-miRNA over pre-siRNA substrates, and dsRNA-binding cofactors (TRBP/PACT, which bind by mutual exclusion) stabilize the enzyme-substrate complex and govern guide-strand selection fidelity, with DICER, TRBP, and Argonaute2 assembling into the RISC-loading complex (PMID:20932845, PMID:21528450, PMID:25557550). Beyond canonical dicing, DICER carries out catalysis-independent and noncanonical roles: it is recruited to UV-damaged chromatin via ZRF1/PARP1 to promote chromatin decondensation and recruits the methyltransferase MMSET to deposit H4K20me2 enabling XPA loading during nucleotide excision repair (PMID:28402505, PMID:29233865), it resolves R-loops by cleaving the RNA strand of DNA-RNA hybrids independently of DROSHA (PMID:37827159), and a stem-cell-expressed isoform (aviD) dices viral dsRNA to mediate antiviral RNAi (PMID:34244417). DICER abundance and activity are controlled post-transcriptionally by the destabilizing RNA-binding protein AUF1 (PMID:23066106, PMID:26990999), by selective autophagy through the receptor NDP52 (PMID:23143396), by HIF-1α-directed Parkin-mediated ubiquitination (PMID:29251629), and by phosphorylation at conserved serines that tunes its function in vivo (PMID:30593561).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2000 Medium

    Identifying the gene and its domain architecture established DICER1 as a candidate ribonuclease combining a helicase and an RNase module, framing all subsequent mechanistic work.

    Evidence cDNA cloning, sequence analysis, and chromosomal mapping of human DICER1

    PMID:10786632

    Open questions at the time
    • No functional or enzymatic characterization
    • Domain functions inferred from homology only
  2. 2002 High

    Demonstrating that recombinant human Dicer generates ~21-23 nt products from dsRNA established its core endonuclease activity and uncoupled substrate binding from Mg2+-dependent catalysis.

    Evidence In vitro ribonuclease and dsRNA-binding assays with recombinant protein

    PMID:12411504

    Open questions at the time
    • Did not resolve how product length is measured
    • ER co-localization not mechanistically connected to dicing
  3. 2004 High

    Genetic dissection in Drosophila assigned distinct Dicer paralogs to miRNA versus siRNA pathways and to discrete RISC-assembly steps, defining pathway specialization.

    Evidence Loss-of-function mutations in dicer-1/dicer-2 with RNAi and pre-miRNA processing assays

    PMID:15066283

    Open questions at the time
    • Single-Dicer organisms (mammals) handle both pathways differently
    • Molecular basis of substrate discrimination not defined
  4. 2005 High

    Identifying R3D1-L/LOQS as a stable Dicer-1 cofactor that enhances miRNA production established that dsRNA-binding partner proteins are required for efficient biogenesis.

    Evidence Co-IP, in vitro reconstitution, and RNAi knockdown in Drosophila S2 cells

    PMID:15985611

    Open questions at the time
    • Mammalian cofactor identity addressed only later
    • Structural basis of cofactor stimulation unknown at this stage
  5. 2007 High

    Mapping the PAZ domain as a dsRNA-end-recognition module and molecular ruler explained how Dicer sets product length.

    Evidence PAZ mutagenesis, binding/cleavage assays, and U1A domain-swap engineering

    PMID:17873886

    Open questions at the time
    • Did not explain 5'-end anchoring contribution
    • Sequence-specific recognition not yet known
  6. 2010 High

    Kinetic analysis showed human Dicer intrinsically favors pre-miRNA over pre-siRNA and that TRBP accelerates dicing by stabilizing enzyme-substrate complexes via its N-terminal dsRBDs.

    Evidence Single- and multiple-turnover Michaelis-Menten kinetics with TRBP domain deletions

    PMID:20932845

    Open questions at the time
    • Structural basis of substrate preference not resolved
    • How TRBP affects fidelity not addressed here
  7. 2011 High

    Discovery of the 5' pocket and '5' counting rule' established a second anchoring mechanism that sets cleavage position ~22 nt from the 5' phosphate.

    Evidence In vitro cleavage assays, 5'-pocket mutagenesis, and Dicer-null ES cell rescue

    PMID:21753850

    Open questions at the time
    • Interplay with PAZ-based 3' counting incompletely resolved
    • Sequence-element contribution not yet identified
  8. 2011 Medium

    Reconstituting the Dicer-TRBP-Ago2 RISC-loading complex from recombinant components defined the minimal machinery for small-RNA loading.

    Evidence In vitro reconstitution of purified recombinant components with loading activity assays

    PMID:21528450

    Open questions at the time
    • Methods-paper context, no independent replication cited
    • Stoichiometry and dynamics of loading not detailed
  9. 2013 High

    EM analysis revealed that substrate identity drives Dicer into productive versus nonproductive conformations, providing a structural rationale for pre-miRNA preference.

    Evidence Electron microscopy and single-particle analysis of Dicer-RNA complexes

    PMID:23624860

    Open questions at the time
    • Low-resolution; atomic contacts unresolved
    • Cofactor-induced changes not atomically defined
  10. 2014 High

    The Dicer-TRBP crystal interface and rescue experiments showed TRBP/PACT bind by mutual exclusion and control guide-strand selection fidelity.

    Evidence Crystal structure, interface mutagenesis, and genome-wide miRNA profiling in Dicer-deficient cells

    PMID:25557550

    Open questions at the time
    • Functional distinction between TRBP and PACT not fully resolved
    • Full-length complex structure not determined
  11. 2014 Medium

    Transcriptome-wide mapping uncovered thousands of 'passive' Dicer-binding sites on mRNAs/lncRNAs that stabilize targets and can sequester Dicer, extending its role beyond canonical small-RNA production.

    Evidence CLIP/RIP mapping with high-throughput sequencing in human cells and C. elegans

    PMID:25416952

    Open questions at the time
    • Functional consequences of most passive sites uncharacterized
    • Mechanism of stabilization unclear
  12. 2014 High

    Identifying the Translin/Trax complex as a pre-miRNA-degrading enzyme competing with Dicer revealed an antagonistic pathway shaping miRNA levels.

    Evidence Chromatographic purification, Dicer-antagonist assay, and genetic/pharmacological TN/TX inhibition

    PMID:25457613

    Open questions at the time
    • Regulation of the Dicer-versus-TN/TX balance unclear
    • Substrate selectivity of TN/TX not fully defined
  13. 2015 Medium

    Nuclear DICER1 was implicated in establishing alternative cleavage and polyadenylation profiles, indicating a role beyond cytoplasmic dicing.

    Evidence Subcellular fractionation with nuclear/cytoplasmic RNA-seq and DICER1 knockdown APA profiling

    PMID:26546131

    Open questions at the time
    • Direct nuclear localization of DICER contested by later work
    • Molecular mechanism of APA control undefined
  14. 2016 High

    Endogenous knock-in reporter mice established that Dicer is exclusively cytoplasmic and does not shuttle to the nucleus, constraining interpretations of nuclear functions.

    Evidence Endogenous epitope-tagged Dicer knock-in mouse, fractionation, and confocal imaging across tissues

    PMID:27254021

    Open questions at the time
    • Reconciliation with reported nuclear/chromatin activities unresolved
    • Possible low-abundance or isoform-specific nuclear pools not excluded by this assay
  15. 2016 Medium

    AUF1 was shown to bind and destabilize DICER1 mRNA, and metformin raises DICER1 by displacing AUF1, linking DICER abundance to senescence control.

    Evidence RIP, AUF1 gain/loss-of-function, mRNA half-life measurement, and DICER1-dependent rescue

    PMID:23066106 PMID:26990999

    Open questions at the time
    • Signal transduction connecting metformin to AUF1 localization incomplete
    • Physiological breadth of this regulation unknown
  16. 2017 Medium

    DICER was shown to be degraded by selective autophagy via NDP52 and by HIF-1α-directed Parkin ubiquitination, defining post-translational control of the miRNA pathway with consequences for EMT and metastasis.

    Evidence Co-IP, ubiquitination assays, autophagy/NDP52 manipulation, and in vivo metastasis model

    PMID:23143396 PMID:29251629

    Open questions at the time
    • Crosstalk between autophagy and ubiquitination routes unclear
    • Signals triggering DICER turnover incompletely mapped
  17. 2017 Medium

    Recruitment of DICER to UV-damaged chromatin via ZRF1/PARP1 and recruitment of MMSET to deposit H4K20me2 established catalysis-independent roles in nucleotide excision repair.

    Evidence Chromatin recruitment assays, knockdowns, PARP1 inhibition, H4K20me2 ChIP, XPA recruitment, and DICER catalytic mutant analysis

    PMID:28402505 PMID:29233865

    Open questions at the time
    • How a cytoplasmic enzyme accesses chromatin unresolved given cytoplasmic-only data
    • Direct DICER-MMSET interaction not structurally defined
  18. 2017 Medium

    The helicase domain was shown to mediate interactions with PKR and other dsRNA-binding helicases, and its deletion confers RNAi-independent, PKR-dependent antiviral activity.

    Evidence Viral-infection interactome and helicase-domain deletion functional assays

    PMID:33984068

    Open questions at the time
    • Direct versus indirect helicase-PKR contacts not resolved
    • In vivo relevance during natural infection not established
  19. 2018 High

    Phosphomimetic knock-in mice demonstrated that constitutive Dicer1 phosphorylation at conserved serines causes lethality and accelerated aging, showing phosphorylation oscillation tightly regulates Dicer function.

    Evidence S1712D/S1836D phosphomimetic knock-in mice with phenotyping and miRNA profiling

    PMID:30593561

    Open questions at the time
    • Kinases/phosphatases controlling these sites not identified
    • Molecular effect of phosphorylation on dicing not defined
  20. 2021 High

    Discovery of the aviD isoform in tissue stem cells established that human Dicer can dice viral dsRNA to mediate protective antiviral RNAi.

    Evidence Isoform characterization, in vitro viral dsRNA dicing, and infection assays in stem cells

    PMID:34244417

    Open questions at the time
    • Regulation of aviD isoform expression unclear
    • Breadth of viruses controlled and in vivo significance limited
  21. 2022 High

    Cryo-EM of mammalian Dicer and the Drosophila Dicer-1/Loqs-PB heterodimer defined a helicase-domain-imposed closed state and a complete cleavage cycle, with TARBP2 stimulating the open, cleavage-competent transition.

    Evidence Cryo-EM structures, DExD/H domain deletion/mutagenesis, TARBP2 assays, and mouse genetic models

    PMID:36182693 PMID:36332606

    Open questions at the time
    • Conformational dynamics in cells not directly observed
    • How phosphorylation/cofactors modulate these states unresolved
  22. 2023 High

    Massively parallel substrate assays defined the GYM sequence motif recognized by the C-terminal dsRBD as a determinant that can override the counting rules and is disrupted by the cancer-associated R1855L substitution; a position-22 bulge similarly enhances cleavage accuracy.

    Evidence High-throughput pre-miRNA/shRNA variant cleavage assays, dsRBD mutagenesis, and in vivo miRNA repertoire analysis

    PMID:35440644 PMID:36813957

    Open questions at the time
    • Genome-wide prevalence of GYM-dependent processing not fully quantified
    • Disease mechanism of dsRBD mutations beyond cleavage defects not detailed
  23. 2023 High

    DICER was shown to act as an R-loop resolvase by cleaving the RNA strand of DNA-RNA hybrids independently of DROSHA, expanding its role into genome stability.

    Evidence In vitro R-loop cleavage with recombinant DICER and RNase catalytic mutant cell lines with R-loop accumulation assays

    PMID:37827159

    Open questions at the time
    • How DICER is targeted to specific R-loops unknown
    • Reconciliation with exclusively cytoplasmic localization data unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DICER's nuclear/chromatin-associated and genome-stability functions are reconciled with its reported exclusively cytoplasmic localization, and what kinases and signals control its phosphorylation and turnover, remain open.
  • Mechanism of chromatin/R-loop access by a cytoplasmic enzyme unresolved
  • Upstream regulatory kinases/phosphatases unidentified
  • Physiological contexts selecting noncanonical functions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 4 GO:0003723 RNA binding 3 GO:0016787 hydrolase activity 2 GO:0140657 ATP-dependent activity 1
Localization
GO:0005783 endoplasmic reticulum 1 GO:0005829 cytosol 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-73894 DNA Repair 3 R-HSA-168256 Immune System 2
Partners
AGO2AUF1LOQSNDP52PACTPARK2TARBP2ZRF1
Complex memberships
Dicer-1/Loqs-PB heterodimerRISC-loading complex (DICER-TRBP-AGO2)

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Recombinant human Dicer (218 kDa) generates ~21-23 nt products from dsRNA in a Mg2+-dependent manner; Mg2+ is required for dsRNase activity but not for dsRNA binding, uncoupling the two reaction steps. ATP is dispensable for dsRNase activity in vitro. The C-terminal putative dsRNA-binding domain binds dsRNA in vitro. In mammalian cells, Dicer co-localizes with calreticulin at the endoplasmic reticulum. In vitro ribonuclease assay with recombinant protein, dsRNA-binding assay, co-localization by immunofluorescence with ER marker calreticulin The EMBO journal High 12411504
2004 In Drosophila, Dicer-1 is specifically required for processing of miRNA precursors, whereas Dicer-2 is required for processing of siRNA precursors. Both Dicer-1 and Dicer-2 are required for siRNA-directed mRNA cleavage, but the RNase III activity of Dicer-2 is not required for this step. Dicer-1 and Dicer-2 facilitate distinct steps in siRISC assembly. Dicer-1, but not Dicer-2, is essential for miRISC-directed translation repression. Genetic loss-of-function mutations in dicer-1 and dicer-2 in Drosophila, RNAi functional assays, pre-miRNA processing assays Cell High 15066283
2005 Drosophila Dicer-1 forms a stable complex with the dsRNA-binding protein R3D1-L (LOQS) in vitro and in vivo. R3D1-L depletion by RNAi causes accumulation of pre-miRNA, and recombinant R3D1-L enhances miRNA production by Dicer-1 in vitro, demonstrating that R3D1-L acts as a co-factor for Dicer-1 in miRNA biogenesis. Co-immunoprecipitation, in vitro reconstitution of miRNA processing with recombinant proteins, RNAi knockdown in S2 cells Genes & development High 15985611
2007 The PAZ domain of Dicer confers dsRNA end recognition and acts as a molecular ruler for RNA product length. Point mutations defining the dsRNA-binding surface of PAZ reveal a protein loop important for cleavage of substrates with perfect or imperfect base pairing. Replacing the PAZ domain with a U1A RNA-binding domain creates an enzyme with altered end-recognition specificity and altered RNA product length. PAZ domain mutagenesis, RNA-binding assays, in vitro cleavage assays, domain-swap engineering Nature structural & molecular biology High 17873886
2010 Human Dicer processes pre-miRNA substrates >100-fold faster than pre-siRNA substrates under multiple-turnover conditions (Michaelis-Menten kinetics). TRBP enhances dicing of both substrate types by stabilizing Dicer-substrate complexes, and this stimulation requires the two N-terminal dsRNA-binding domains of TRBP. In vitro cleavage kinetics (single- and multiple-turnover Michaelis-Menten analysis), TRBP domain deletion analysis Journal of molecular biology High 20932845
2011 Human Dicer uses a '5' counting rule' to determine cleavage sites: it anchors the 5'-phosphorylated end of the pre-miRNA substrate via a novel basic motif called the '5' pocket', and the cleavage site is determined mainly by the distance (~22 nt) from the 5' end. Mutations in the 5' pocket reduce processing efficiency and alter cleavage sites in vitro, and impair miRNA biogenesis in Dicer-null ES cells rescued with 5'-pocket mutant Dicer. In vitro cleavage assays, site-directed mutagenesis of 5' pocket residues, rescue of Dicer-null ES cells with mutant Dicer Nature High 21753850
2011 The human RISC-loading complex (RLC) comprises Dicer, TRBP, and Argonaute2 (Ago2). This trimolecular complex can be reconstituted in vitro from recombinant components, and the assembled RLC is biochemically active in small RNA loading. In vitro reconstitution of purified recombinant human Dicer, TRBP, and Ago2; biochemical activity assays Methods in molecular biology Medium 21528450
2012 Selective autophagy degrades DICER and AGO2 as miRNA-free entities via the selective autophagy receptor NDP52. Autophagy is required for continued loading of miRNA into AGO2 and for homeostasis of the miRNA pathway. NDP52 and autophagy also post-transcriptionally regulate DICER mRNA. Co-immunoprecipitation identifying NDP52 as DICER/AGO2 autophagy receptor, autophagy inhibition and NDP52 knockdown with miRNA activity/loading readouts Nature cell biology High 23143396
2012 The RNA-binding protein AUF1 binds the DICER1 mRNA (coding region and 3'UTR) and destabilizes it. Silencing AUF1 lengthens DICER1 mRNA half-life and increases Dicer protein levels; overexpressing AUF1 reduces DICER1 mRNA and protein. Reduction of Dicer by AUF1 diminishes mature miRNA levels without affecting pre-miRNA levels. RNA immunoprecipitation (RIP) of AUF1-DICER1 mRNA complex, AUF1 knockdown and overexpression with mRNA half-life measurement and Dicer/miRNA quantification Nucleic acids research Medium 23066106
2013 Human Dicer adopts substrate-specific structural conformations: pre-siRNAs are trapped in a nonproductive conformation, whereas pre-miRNAs and dsRNA-binding protein cofactors induce structural changes enabling productive substrate recognition in the central catalytic channel. Electron microscopy and single-particle analysis of Dicer-RNA complexes Nature structural & molecular biology High 23624860
2014 The crystal structure of the human Dicer-TRBP interface reveals the structural basis of their interaction. Interface residues conserved between TRBP and PACT show that these proteins bind Dicer in a similar manner by mutual exclusion. A catalytically active Dicer that cannot bind TRBP or PACT shows selective defects in guide strand selection when introduced into Dicer-deficient cells, demonstrating the role of these cofactors in gene-silencing fidelity. Crystal structure of Dicer-TRBP interface, interface mutagenesis, Dicer-deficient cell rescue experiments, genome-wide miRNA profiling Molecular cell High 25557550
2014 Thousands of Dicer-binding sites reside on mRNAs and lncRNAs beyond miRNA loci. Most of these 'passive' Dicer-binding sites harbor small hairpins within intact transcripts and generally stabilize target expression rather than triggering small RNA production. Passive sites can sequester Dicer and reduce microRNA expression. Biochemical mapping of Dicer-binding sites by CLIP/RIP in human cells and C. elegans, high-throughput sequencing Cell Medium 25416952
2014 The Translin/Trax (TN/TX) ribonuclease complex functions as a pre-miRNA-degrading enzyme that competes with Dicer-mediated pre-miRNA processing. In wild-type Dicer backgrounds, processing dominates; in Dicer-deficient contexts, TN/TX broadly suppresses miRNA levels. Inhibition of TN/TX partially rescues miRNA levels and tumor suppression in Dicer-haploinsufficient cells. Unbiased chromatographic purification and identification of pre-miRNA degrading activity, Dicer-antagonist assay, genetic and pharmacological inhibition of TN/TX Cell reports High 25457613
2015 Nuclear DICER1 contributes to the establishment of subcellular alternative cleavage and polyadenylation (APA) profiles. This function is in addition to cytoplasmic miRNA-mediated destabilization of APA mRNA isoforms, and DICER1 affects polyadenylation site choice in the nucleus. Subcellular fractionation, RNA-seq of nuclear vs. cytoplasmic fractions, DICER1 knockdown with APA profiling Genome research Medium 26546131
2016 Metformin increases DICER1 protein levels through a post-transcriptional mechanism involving the RNA-binding protein AUF1: metformin alters AUF1 subcellular localization, disrupting its interaction with DICER1 mRNA, stabilizing DICER1 mRNA and allowing DICER1 to accumulate. Increased DICER1 decreases cellular senescence in a DICER1-dependent manner. AUF1-DICER1 mRNA interaction assay, subcellular fractionation of AUF1, DICER1 mRNA stability measurement, DICER1 knockdown rescue of metformin phenotype Aging cell Medium 26990999
2016 Endogenous mouse Dicer is an exclusively cytoplasmic protein in all examined primary cell types, adult tissues, and throughout embryogenesis. No fraction of Dicer shuttles to or from the nucleus, and neither FGF signaling nor DNA damage induces Dicer nuclear translocation. Endogenous epitope-tagged Dicer knock-in mouse, biochemical fractionation, confocal immunofluorescence microscopy PLoS genetics High 27254021
2017 HIF-1α interacts directly with Dicer protein and downregulates Dicer expression by facilitating its ubiquitination by the E3 ubiquitin ligase Parkin, thereby promoting autophagy-mediated degradation of Dicer. This suppresses maturation of miRNAs including let-7 and miR-200b, and facilitates epithelial-mesenchymal transition and metastasis. Co-immunoprecipitation of HIF-1α and Dicer, ubiquitination assay identifying Parkin as E3 ligase, autophagy inhibition rescue experiments, in vivo metastasis model The Journal of clinical investigation Medium 29251629
2017 The human DICER helicase domain is required for interaction with PKR (protein kinase RNA-activated) and other dsRNA-binding proteins and RNA helicases (including DHX9 and ADAR-1) during alphavirus infection. Deletion of the helicase domain confers antiviral properties to DICER in an RNAi-independent, PKR-dependent manner. Proteomics/interactome of DICER during viral infection, DICER helicase domain deletion mutant analysis, PKR-dependent antiviral assay PLoS pathogens Medium 33984068
2017 DICER is recruited to chromatin at UV-damaged sites in a ZRF1-mediated manner. DICER and ZRF1 together promote chromatin decondensation during nucleotide excision repair (NER) via PARP1. This chromatin decondensation function of DICER is independent of its catalytic RNase activity. Chromatin recruitment assay after UV irradiation, ZRF1 knockdown, PARP1 inhibition, DICER catalytic mutant analysis Nucleic acids research Medium 28402505
2017 DICER mediates recruitment of the methyltransferase MMSET to DNA damage sites during NER. MMSET catalyzes dimethylation of histone H4 at lysine 20 (H4K20me2) at DNA damage sites, and this mark facilitates recruitment of the NER factor XPA. DICER and MMSET knockdown during NER, H4K20me2 ChIP at UV damage sites, XPA recruitment assay The Journal of cell biology Medium 29233865
2018 Constitutive phosphorylation of mouse Dicer1 at conserved serines 1712 and 1836 (phosphomimetic S→D knock-in) results in highly penetrant postnatal lethality, accelerated aging, infertility, altered metabolism-associated miRNAs, and a hypermetabolic phenotype. This demonstrates that oscillation of Dicer1 phosphorylation tightly regulates its function in mammals. Phosphomimetic knock-in mouse models (S1712D and S1836D, single and dual), phenotypic characterization, miRNA profiling Proceedings of the National Academy of Sciences of the United States of America High 30593561
2021 A specific isoform of human Dicer, named antiviral Dicer (aviD), expressed in tissue stem cells, cleaves viral double-stranded RNA to orchestrate antiviral RNAi, protecting stem cells from RNA viruses including Zika virus and SARS-CoV-2. Identification and characterization of aviD isoform, in vitro dicing assays of viral dsRNA, viral infection assays in stem cells Science (New York, N.Y.) High 34244417
2022 The DExD/H helicase domain of mammalian Dicer has a helicase-unrelated structural function: it locks Dicer in a closed state that facilitates pre-miRNA precursor selection. Transition to a cleavage-competent open state is stimulated by the Dicer-binding protein TARBP2. Loss of the DExD/H domain or mutations in it unlock the closed state, reduce substrate selectivity, and activate RNAi. Cryo-EM structures of murine Dicer-pre-miRNA complexes reveal this mechanism. Cryo-EM structures of murine Dicer with pre-miRNA substrates, DExD/H domain deletion and mutagenesis, TARBP2 functional assays, mouse genetic models (ATPase-dead and domain-deleted) Molecular cell High 36332606
2022 Six cryo-EM structures of Drosophila Dicer-1 in complex with its partner Loqs-PB reveal a complete reaction cycle: pre-miRNA binds a rare open conformation of the Dicer-1/Loqs-PB heterodimer; Dicer-1 dsRBD and three Loqs-PB dsRBDs form a belt that distorts the RNA helix to place scissile bonds in RNase III active sites; cleavage shifts dsRBDs and partially closes Dicer-1 to promote product release. Cryo-EM structures of six Dicer-1/Loqs-PB states, structural analysis of active site positioning Molecular cell High 36182693
2022 A single-nucleotide bulge at position 22 (22-bulge) in shRNAs and pre-miRNAs facilitates DICER cleavage activity and enhances accuracy of miRNA biogenesis and gene silencing. High-throughput DICER cleavage assays on >20,000 shRNA variants, mutational analysis of 22-bulge in pre-miRNAs Nature communications High 35440644
2023 Human DICER recognizes a conserved cis-acting sequence element near the cleavage site of pre-miRNAs, termed the 'GYM motif' (paired G, paired pyrimidine, mismatched C or A). The GYM motif promotes cleavage at a specific position and can override the 5' and 3' counting rules. The C-terminal dsRNA-binding domain (dsRBD) of DICER recognizes the GYM motif; alterations in the dsRBD reduce processing and change cleavage sites in a motif-dependent fashion. The cancer-associated R1855L substitution in the dsRBD strongly impairs GYM motif recognition. Massively parallel pre-miRNA variant assays with human DICER, dsRBD mutagenesis, in vitro cleavage assays, in vivo miRNA repertoire analysis in cells Nature High 36813957
2023 DICER cleaves the RNA moiety within R-loops (DNA-RNA hybrids with displaced ssDNA), functioning as an R-loop resolvase. A DICER RNase mutant impaired in R-loop processing causes strong accumulation of R-loops in cells. This activity is independent of DROSHA. In vitro R-loop cleavage biochemical assay with recombinant DICER, DICER RNase catalytic mutant cell lines, R-loop accumulation assay (S9.6 antibody-based) Molecular cell High 37827159
2000 Cloning and sequencing of human DICER1 (originally named HERNA) reveals a 1924 amino acid protein with an RNA-helicase DEXH-box motif at the amino terminus and an RNase motif at the carboxy terminus, mapped to chromosome 14q31. It is homologous to C. elegans K12H4.8. cDNA library cloning, sequence analysis, chromosomal mapping by hybrid panel PCR and radiation hybrid panels Biochimica et biophysica acta Medium 10786632

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways. Cell 994 15066283
2007 Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis. Circulation research 652 17540974
2014 DICER1: mutations, microRNAs and mechanisms. Nature reviews. Cancer 432 25176334
2011 Dicer recognizes the 5' end of RNA for efficient and accurate processing. Nature 387 21753850
2002 Ribonuclease activity and RNA binding of recombinant human Dicer. The EMBO journal 348 12411504
2005 Dicer-1 and R3D1-L catalyze microRNA maturation in Drosophila. Genes & development 243 15985611
2007 Structural determinants of RNA recognition and cleavage by Dicer. Nature structural & molecular biology 236 17873886
2012 Selective autophagy degrades DICER and AGO2 and regulates miRNA activity. Nature cell biology 213 23143396
2014 Dicer-TRBP complex formation ensures accurate mammalian microRNA biogenesis. Molecular cell 210 25557550
2017 Molecular mechanisms of Dicer: endonuclease and enzymatic activity. The Biochemical journal 168 28473628
2016 Metformin-mediated increase in DICER1 regulates microRNA expression and cellular senescence. Aging cell 159 26990999
2008 Role of Dicer in posttranscriptional RNA silencing. Current topics in microbiology and immunology 147 18268840
2010 Osteoclast-specific Dicer gene deficiency suppresses osteoclastic bone resorption. Journal of cellular biochemistry 143 20039311
2014 Germ-line and somatic DICER1 mutations in pineoblastoma. Acta neuropathologica 125 25022261
2010 Substrate-specific kinetics of Dicer-catalyzed RNA processing. Journal of molecular biology 120 20932845
2019 Ten years of DICER1 mutations: Provenance, distribution, and associated phenotypes. Human mutation 111 31342592
2018 DICER1 Syndrome: DICER1 Mutations in Rare Cancers. Cancers 110 29762508
2009 Dicer-like (DCL) proteins in plants. Functional & integrative genomics 101 19221817
2021 An isoform of Dicer protects mammalian stem cells against multiple RNA viruses. Science (New York, N.Y.) 96 34244417
2014 Derivation and characterization of Dicer- and microRNA-deficient human cells. RNA (New York, N.Y.) 96 24757167
2013 Dicer-2 processes diverse viral RNA species. PloS one 95 23424633
2018 Noncanonical functions of microRNA pathway enzymes - Drosha, DGCR8, Dicer and Ago proteins. FEBS letters 94 30025156
2014 A variety of dicer substrates in human and C. elegans. Cell 92 25416952
2018 Dicer in Macrophages Prevents Atherosclerosis by Promoting Mitochondrial Oxidative Metabolism. Circulation 91 29748186
2017 Dicer and microRNAs protect adult dopamine neurons. Cell death & disease 80 28542144
2013 Substrate-specific structural rearrangements of human Dicer. Nature structural & molecular biology 77 23624860
2009 Dicer-dependent microRNA pathway controls invariant NKT cell development. Journal of immunology (Baltimore, Md. : 1950) 77 19625646
2010 Absence of DICER in monocytes and its regulation by HIV-1. The Journal of biological chemistry 72 20584909
2023 Sequence determinant of small RNA production by DICER. Nature 71 36813957
2019 Expanding the spectrum of dicer1-associated sarcomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 68 31537896
2017 Dicer-independent processing of small RNA duplexes: mechanistic insights and applications. Nucleic acids research 68 28977573
2011 Expression of the ribonucleases Drosha, Dicer, and Ago2 in colorectal carcinomas. Virchows Archiv : an international journal of pathology 68 21769619
2015 Subcellular RNA profiling links splicing and nuclear DICER1 to alternative cleavage and polyadenylation. Genome research 67 26546131
2022 Structural and functional basis of mammalian microRNA biogenesis by Dicer. Molecular cell 65 36332606
2017 HIF-1α promotes autophagic proteolysis of Dicer and enhances tumor metastasis. The Journal of clinical investigation 63 29251629
2008 The mechanism of RNase III action: how dicer dices. Current topics in microbiology and immunology 63 18268841
2009 Role of Dicer in female fertility. Trends in endocrinology and metabolism: TEM 61 19646895
2012 RNA-binding protein AUF1 represses Dicer expression. Nucleic acids research 60 23066106
2010 Dicer is required for Sertoli cell function and survival. The International journal of developmental biology 60 19876815
2001 A comprehensive analysis of MNG1, TCO1, fPTC, PTEN, TSHR, and TRKA in familial nonmedullary thyroid cancer: confirmation of linkage to TCO1. The Journal of clinical endocrinology and metabolism 58 11502798
2011 Dysregulated expression of dicer and drosha in breast cancer. Pathology oncology research : POR 55 21898071
2006 The RNAi pathway initiated by Dicer-2 in Drosophila. Cold Spring Harbor symposia on quantitative biology 54 17381278
2012 Dicer-processed small RNAs: rules and exceptions. Journal of experimental zoology. Part B, Molecular and developmental evolution 53 23165937
2006 An unusual Dicer-like1 protein fuels the RNA interference pathway in Trypanosoma brucei. RNA (New York, N.Y.) 53 17053086
2016 Biogenesis of diverse plant phasiRNAs involves an miRNA-trigger and Dicer-processing. Journal of plant research 52 27900550
2022 Structural basis of microRNA biogenesis by Dicer-1 and its partner protein Loqs-PB. Molecular cell 51 36182693
2016 Macrocephaly associated with the DICER1 syndrome. Genetics in medicine : official journal of the American College of Medical Genetics 49 27441995
2018 Dicer-like Enzymes with Sequence Cleavage Preferences. Cell 48 29551264
2021 DICER: structure, function, and regulation. Biophysical reviews 46 35059029
2014 Rescuing dicer defects via inhibition of an anti-dicing nuclease. Cell reports 44 25457613
2016 Runx2/DICER/miRNA Pathway in Regulating Osteogenesis. Journal of cellular physiology 43 27064596
2010 Reduction of Dicer impairs Schwann cell differentiation and myelination. Journal of neuroscience research 42 20648646
2022 Secondary structure RNA elements control the cleavage activity of DICER. Nature communications 41 35440644
2014 Dicer expression and microRNA dysregulation associate with aggressive features in thyroid cancer. Surgery 41 25456905
2000 Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase. Biochimica et biophysica acta 41 10786632
2021 Modulation of MicroRNA Processing by Dicer via Its Associated dsRNA Binding Proteins. Non-coding RNA 40 34564319
2015 Dgcr8 and Dicer are essential for sex chromosome integrity during meiosis in males. Journal of cell science 39 25934699
2009 X chromosome inactivation in the absence of Dicer. Proceedings of the National Academy of Sciences of the United States of America 39 19164542
2019 Dicer functions transcriptionally and posttranscriptionally in a multilayer antiviral defense. Proceedings of the National Academy of Sciences of the United States of America 38 30674672
2021 A Glimpse of "Dicer Biology" Through the Structural and Functional Perspective. Frontiers in molecular biosciences 37 34026825
2015 Sensing viral RNAs by Dicer/RIG-I like ATPases across species. Current opinion in immunology 37 25658360
2013 MiR-192 directly binds and regulates Dicer1 expression in neuroblastoma. PloS one 37 24223844
2023 Dicer structure and function: conserved and evolving features. EMBO reports 36 37310138
2019 Design, mechanism, delivery and therapeutics of canonical and Dicer-substrate siRNA. Asian journal of pharmaceutical sciences 36 32104477
2018 DICER1 gene mutations in endocrine tumors. Endocrine-related cancer 36 29330195
2020 Dicing the Disease with Dicer: The Implications of Dicer Ribonuclease in Human Pathologies. International journal of molecular sciences 35 33007856
2020 Gene of the month: DICER1: ruler and controller. Journal of clinical pathology 35 33293352
2017 DICER and ZRF1 contribute to chromatin decondensation during nucleotide excision repair. Nucleic acids research 35 28402505
2016 Germline and somatic DICER1 mutations in familial and sporadic liver tumors. Journal of hepatology 35 28012864
2018 DICER1 hot-spot mutations in ovarian gynandroblastoma. Histopathology 34 29660837
2016 Production of small RNAs by mammalian Dicer. Pflugers Archiv : European journal of physiology 34 27048428
2020 Chronic Dicer1 deficiency promotes atrophic and neovascular outer retinal pathologies in mice. Proceedings of the National Academy of Sciences of the United States of America 32 31964819
2007 Dicer expression and localization in post-mitotic neurons. Brain research 32 17888888
2023 DICER ribonuclease removes harmful R-loops. Molecular cell 31 37827159
2019 Imaging of DICER1 syndrome. Pediatric radiology 31 31620849
2016 Gynecologic Manifestations of the DICER1 Syndrome. Surgical pathology clinics 30 27241106
2024 Expanding Our Knowledge of DICER1 Gene Alterations and Their Role in Thyroid Diseases. Cancers 29 38254836
2010 DICER1 expression and outcomes in endometrioid endometrial adenocarcinoma. Cancer 28 21425145
2020 GABPA-dependent down-regulation of DICER1 in follicular thyroid tumours. Endocrine-related cancer 27 32163919
2018 DAWDLE Interacts with DICER-LIKE Proteins to Mediate Small RNA Biogenesis. Plant physiology 27 29784765
2015 Deregulation of dicer and mir-155 expression in liposarcoma. Oncotarget 25 25888631
2021 Human DICER helicase domain recruits PKR and modulates its antiviral activity. PLoS pathogens 24 33984068
2013 Evolution of RNA interference proteins dicer and argonaute in Basidiomycota. Mycologia 24 23928424
2017 Pediatric imaging in DICER1 syndrome. Pediatric radiology 23 28474256
2017 DICER- and MMSET-catalyzed H4K20me2 recruits the nucleotide excision repair factor XPA to DNA damage sites. The Journal of cell biology 23 29233865
2016 Endogenous Mouse Dicer Is an Exclusively Cytoplasmic Protein. PLoS genetics 23 27254021
2007 Decreased expression of DICER1 in gastric cancer. Chinese medical journal 23 18167183
2022 The Effect of Dicer Knockout on RNA Interference Using Various Dicer Substrate Small Interfering RNA (DsiRNA) Structures. Genes 21 35327991
2022 APE1 controls DICER1 expression in NSCLC through miR-33a and miR-130b. Cellular and molecular life sciences : CMLS 21 35876890
2021 Molecular characterization of DICER1-mutated pituitary blastoma. Acta neuropathologica 21 33644822
2013 Dicer's role as an antiviral: still an enigma. Current opinion in immunology 21 24556400
2017 Biallelic Dicer1 Loss Mediated by aP2-Cre Drives Angiosarcoma. Cancer research 20 28916654
2021 Role of Dicer-Dependent RNA Interference in Regulating Mycoparasitic Interactions. Microbiology spectrum 19 34549988
2018 Dicer regulates Nosema ceranae proliferation in honeybees. Insect molecular biology 18 30171639
2015 Low DICER1 expression is associated with poor clinical outcome in adrenocortical carcinoma. Oncotarget 18 26087193
2018 Constitutive Dicer1 phosphorylation accelerates metabolism and aging in vivo. Proceedings of the National Academy of Sciences of the United States of America 17 30593561
2017 New roles for Dicer in the nucleolus and its relevance to cancer. Cell cycle (Georgetown, Tex.) 17 28846478
2017 Role of Dicer1 in thyroid cell proliferation and differentiation. Cell cycle (Georgetown, Tex.) 17 28933615
2013 Dicer in immune cell development and function. Immunological investigations 17 24303839
2011 Purification and assembly of human Argonaute, Dicer, and TRBP complexes. Methods in molecular biology (Clifton, N.J.) 17 21528450

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