Dicer is an endoribonuclease in the RNase III family that cleaves double-stranded RNA (dsRNA) and pre-microRNA (miRNA) into short double-stranded RNA fragments called small interfering RNA (siRNA) about 20-25 nucleotides long, usually with a two-base overhang on the 3' end. Dicer contains two RNase III domains and one PAZ domain; the distance between these two regions of the molecule is determined by the length and angle of the connector helix and may influence the length of the siRNAs it produces.[1] Dicers interact with several partner proteins (TRBP in humans, R2D2, Loqs in Drosophila). These partner proteins could play a role in dictating the substrate specificity of Dicer proteins to their substrates. [2]
Dicer facilitates the formation of the RNA-induced silencing complex (RISC), whose catalytic component argonaute is an endonuclease capable of degrading messenger RNA (mRNA). The human version of this gene is DICER1.
Dicer and other miRNA processing enzymes may be important in cancer prognosis.[3] When researchers in British Columbia sequenced the genomes of rare ovarian, uterine, and testicular tumours, they have found that the same fundamental mutation in the DICER gene showed up as the common process underlying all of the different cancers they have examined. The DICER gene regulates the development and behavior of normal cells in the body, and the mutation of this gene causes this regulating ability to be warped, producing cancerous cells. [4]
Dicer was given its name by a Emily Bernstein, graduate student in Greg Hannon's lab at Cold Spring Harbor Laboratory, who first demonstrated the enzyme's dsRNA "dicing" activity.[5]
In the moss Physcomitrella patens DCL1b, one of four DICER proteins, is not involved in miRNA biogenesis but in dicing miRNA target transcripts. Thus, a novel mechanism for regulation of gene expression, the epigenetic silencing of genes by miRNAs, was discovered.[6][7]