Endoribonuclease Dicer

Function

Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing. Cleaves naturally occurring long dsRNAs and short hairpin pre-microRNAs (miRNA) into fragments of twenty-one to twenty-three nucleotides with 3' overhang of two nucleotides, producing respectively short interfering RNAs (siRNA) and mature microRNAs. SiRNAs and miRNAs serve as guide to direct the RNA-induced silencing complex (RISC) to complementary RNAs to degrade them or prevent their translation. Gene silencing mediated by siRNAs, also called RNA interference, controls the elimination of transcripts from mobile and repetitive DNA elements of the genome but also the degradation of exogenous RNA of viral origin for instance. The miRNA pathway on the other side is a mean to specifically regulate the expression of target genes.

Classification

Family (Pfam)

PF00270 DEAD, PF03368 Dicer_dimer, PF20932 Dicer_dsRBD, PF20930 Dicer_PBD, PF20931 Dicer_platform, PF00271 Helicase_C, PF02170 PAZ, PF00636 Ribonuclease_3

InterPro

DEAD/DEAH_box_helicase_dom, Dicer_dimer_sf, Dicer_dimerisation, DICER_DSRM, Dicer_PBD, Dicer_platform, dsRBD_dom, Helicase_ATP-bd, Helicase_C-like, P-loop_NTPase, PAZ_dom, PAZ_dom_sf, RNase_III_dom, RNase_III_sf

Functional cluster

Mixed Regulatory & Membrane Proteins

Experimental structures · PDB · 16

• 2EB1 X-ray 2.00A
• 4NGB X-ray 2.25A
• 4NGC X-ray 2.10A
• 4NGD X-ray 1.96A
• 4NGF X-ray 3.10A
• 4NGG X-ray 2.60A
• 4NH3 X-ray 2.62A
• 4NH5 X-ray 2.55A
• 4NH6 X-ray 2.55A
• 4NHA X-ray 3.40A
• 4WYQ X-ray 3.20A
• 5ZAK EM 4.40A
• … and 4 more

A predicted model is available from AlphaFold.

Gene Ontology · 36

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0070062 extracellular exosome
• GO:0005634 nucleus
• GO:0048471 perinuclear region of cytoplasm
• GO:0016442 RISC complex
• GO:0070578 RISC-loading complex
• GO:0005524 ATP binding
• GO:0004530 deoxyribonuclease I activity
• GO:0003725 double-stranded RNA binding
• GO:0004386 helicase activity
• GO:0046872 metal ion binding
• GO:0070883 pre-miRNA binding
• GO:0019904 protein domain specific binding
• GO:0004525 ribonuclease III activity
• GO:0003723 RNA binding
• GO:0004521 RNA endonuclease activity
• GO:0035197 siRNA binding
• GO:0006309 apoptotic DNA fragmentation
• GO:0098795 global gene silencing by mRNA cleavage
• GO:0010586 miRNA metabolic process
• GO:0035196 miRNA processing
• GO:0010629 negative regulation of gene expression
• GO:0010626 negative regulation of Schwann cell proliferation
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0032720 negative regulation of tumor necrosis factor production
• GO:0010804 negative regulation of tumor necrosis factor-mediated signaling pathway
• GO:0021675 nerve development
• GO:0048812 neuron projection morphogenesis
• GO:0032290 peripheral nervous system myelin formation
• GO:0031643 positive regulation of myelination
• GO:0014040 positive regulation of Schwann cell differentiation
• GO:0031054 pre-miRNA processing
• GO:0070922 RISC complex assembly
• GO:0030422 siRNA processing
• GO:0016078 tRNA decay

Disease associations

• goiter, multinodular 1, with or without Sertoli-Leydig cell tumors MONDO:0007681
• rhabdomyosarcoma, embryonal, 2 MONDO:0859046
• pleuropulmonary blastoma MONDO:0011014
• global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome MONDO:0018445

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Endoribonuclease Dicer 1.00
• Endoribonuclease Dicer 1.00
• Endoribonuclease Dicer 1.00
• Endoribonuclease Dicer 0.99
• Endoribonuclease Dicer-L 0.99
• Endoribonuclease Dicer-S 0.98
• Endoribonuclease Dicer 0.98
• Endoribonuclease Dicer 0.97
• Ubiquitin carboxyl-terminal hydrolase 9X 0.76
• Ubiquitin carboxyl-terminal hydrolase 9X 0.76
• Cleavage and polyadenylation specificity factor subunit 3 0.73
• Cleavage and polyadenylation specificity factor subunit 3 0.72

Co-cited proteins · studied together in the literature

• RISC-loading complex subunit TARBP2 12 shared papers
• RNA 5'-monophosphate methyltransferase 1 shared papers
• Transforming growth factor-beta receptor-associated protein 1 1 shared papers
• Protein argonaute-2 10 shared papers
• RISC-loading complex subunit TARBP2 2 shared papers
• Interferon-inducible double-stranded RNA-dependent protein kinase activator A 3 shared papers
• Polyunsaturated fatty acid 5-lipoxygenase 1 shared papers
• Polymerase cofactor VP35 1 shared papers
• Piwi-like protein 1 1 shared papers
• Trinucleotide repeat-containing gene 6B protein 2 shared papers
• Transcriptional activator VP30 1 shared papers
• Eukaryotic translation initiation factor 6 1 shared papers

Literature · 39 cited papers

• Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in pleuropulmonary blastoma / DICER1 syndrome: a unique variant of the two-hit tumor suppression model. F1000Research · 2015
• Retraction: A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function. Nat. Genet. · 2016
• Expanding the phenotype of mutations in DICER1: mosaic missense mutations in the RNase IIIb domain of DICER1 cause GLOW syndrome. J. Med. Genet. · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Human RNA methyltransferase BCDIN3D regulates microRNA processing. Cell · 2012
• Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers. N. Engl. J. Med. · 2012
• Extending the phenotypes associated with DICER1 mutations. Hum. Mutat. · 2011
• System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Ebolavirus proteins suppress the effects of small interfering RNA by direct interaction with the mammalian RNA interference pathway. J. Virol. · 2011
• DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors. JAMA · 2011
• … and 27 more in the literature graph