DICER1
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.
Involvement in disease
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.
None
The disease is caused by variants affecting the gene represented in this entry.
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.
None
The disease is caused by variants affecting the gene represented in this entry.
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.
None
The disease is caused by variants affecting the gene represented in this entry.
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.
None
The disease is caused by variants affecting the gene represented in this entry.
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).
Sequence Similarities
Belongs to the helicase family. Dicer subfamily.
Cellular localization
- Cytoplasm
- Cytoplasm
- Perinuclear region
Alternative names
DICER, HERNA, KIAA0928, DICER1, Endoribonuclease Dicer, Helicase with RNase motif, Helicase MOI