DICER1

This gene encodes a protein possessing an RNA helicase motif containing a DEXH box in its amino terminus and an RNA motif in the carboxy terminus. The encoded protein functions as a ribonuclease and is required by the RNA interference and small temporal RNA (stRNA) pathways to produce the active small RNA component that represses gene expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2010]

Dicer 1, Ribonuclease III

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.

Apoptotic DNA fragmentation Source: GO_Central
Conversion of ds siRNA to ss siRNA Source: AgBase
Conversion of ds siRNA to ss siRNA involved in RNA interference Source: BHF-UCL
miRNA loading onto RISC involved in gene silencing by miRNA Source: BHF-UCL
miRNA metabolic process Source: Reactome
Negative regulation of gene expression Source: ARUK-UCL
Negative regulation of Schwann cell proliferation Source: BHF-UCL
Negative regulation of transcription by RNA polymerase II Source: BHF-UCL
Negative regulation of tumor necrosis factor production Source: ARUK-UCL
Nerve development Source: BHF-UCL
Neuron projection morphogenesis Source: BHF-UCL
NIK/NF-kappaB signaling Source: ARUK-UCL
Peripheral nervous system myelin formation Source: BHF-UCL
Positive regulation of myelination Source: BHF-UCL
Positive regulation of Schwann cell differentiation Source: BHF-UCL
Pre-miRNA processing Source: UniProtKB
Production of miRNAs involved in gene silencing by miRNA Source: UniProtKB
Production of siRNA involved in RNA interference Source: UniProtKB
RNA phosphodiester bond hydrolysis Source: GO_Central
RNA phosphodiester bond hydrolysis, endonucleolytic Source: BHF-UCL
siRNA loading onto RISC involved in RNA interference Source: BHF-UCL
Targeting of mRNA for destruction involved in RNA interference Source: UniProtKB
tRNA catabolic process Source: Reactome

Cytoplasm; Perinuclear region

Pleuropulmonary blastoma (PPB):
A rare pediatric intrathoracic neoplasm. The tumor arises from the lung, pleura, or both, and appears to be purely mesenchymal in phenotype. It lacks malignant epithelial elements, a feature that distinguishes it from the classic adult-type pulmonary blastoma. It arises during fetal lung development and is often part of an inherited cancer syndrome. The tumor contain both epithelial and mesenchymal cells. Early in tumorigenesis, cysts form in lung airspaces, and these cysts are lined with benign-appearing epithelium. Mesenchymal cells susceptible to malignant transformation reside within the cyst walls and form a dense layer beneath the epithelial lining. In a subset of patients, overgrowth of the mesenchymal cells produces a sarcoma, a transition that is associated with a poorer prognosis. Some patients have multilocular cystic nephroma, a benign kidney tumor.
Goiter multinodular 1, with or without Sertoli-Leydig cell tumors (MNG1):
A common disorder characterized by nodular overgrowth of the thyroid gland. Some individuals may also develop Sertoli-Leydig cell tumors, usually of the ovary.
Rhabdomyosarcoma, embryonal, 2 (RMSE2):
A form of rhabdomyosarcoma, a highly malignant tumor of striated muscle derived from primitive mesenchymal cells and exhibiting differentiation along rhabdomyoblastic lines. Rhabdomyosarcoma is one of the most frequently occurring soft tissue sarcomas and the most common in children. It occurs in four forms: alveolar, pleomorphic, embryonal and botryoidal rhabdomyosarcomas.
Global developmental delay, lung cysts, overgrowth, and Wilms tumor (GLOW):
A disease characterized by the association of congenital nephromegaly, bilateral Wilms tumor, somatic overgrowth, developmental delay, macrocephaly, and bilateral lung cysts.
DICER1 mutations have been found in uterine cervix embryonal rhabdomyosarcoma, primitive neuroectodermal tumor, Wilms tumor, pulmonary sequestration and juvenile intestinal polyp (PubMed:21882293). Somatic missense mutations affecting the RNase IIIb domain of DICER1 are common in non-epithelial ovarian tumors. These mutations do not abolish DICER1 function but alter it in specific cell types, a novel mechanism through which perturbation of microRNA processing may be oncogenic (PubMed:22187960).