Dicer
From Proteopedia
Dicer
IntroductionDicer is a type of Ribonuclease that processes potentially harmful double-stranded RNA (dsRNA) into microRNA and small-interfering RNA (siRNA) to be used in the process of RNA interference. Dicer is commonly utilized by cells in order to prevent the assimilation of viral DNA into the cells’ genome. The viral DNA is butchered into smaller segments that are each about 21 nucleotides long; the cut take places at the 5’ phosphate and the 3’ hydroxyl, and usually includes a 2 nucleotide overhang. There is a single processing center in HS Dicer implying that there are two catalytic sites which help form products with the 2 3' overhang. These newly formed segments attach themselves to single stranded mRNA which ultimately leads to mRNA degradation by the cell and translational suppression. The dicer enzyme in humans contains three domains: the , , and the .[1] There are three classes of RNase III proteins which are divided into categories called Escherichia coli RNase III, , and Dicer which are given the numbers one, two, and three respectively. The Escherichia coli RNase III class has one domain while the Drosha and dicer have two domains each. There is no evidence of the first class of enzymes in mammals.
StructureHuman Dicer (hDicer) is a . Each chain is a large multidomain enzyme whose C-terminal half includes a PAZ domain, a pair of tandem RNase III domains, and a double-stranded RNA-binding domain.[2] There are four ions that bind to the hDicer RNase IIIb homodimer. There are oxygen ligands bonded to each Magnesium, which create an geometry on each Magnesium. The amino acids present on the oxygen ligands are Glutamic Acid and Aspartic Acid. PathologyMutations involving the dicer protein have been linked to the development of diseases in humans. Conditions such as pleuropulmonary blastoma[3], goiter multinodular[4], and rhabdomyosarcoma[5] are related to dicer malfunction. Pleuropulmonary blastoma, goiter multinodular, cystic nephroma, and Sertoli-Leydig cell tumors are due a mutation in the Dicer1 gene given the name Dicer1 Syndrome. Dicer1 Syndrome is an inherited disorder that causes the risk of malignant tumors and benign tumors to increase. This occurs because short Dicer proteins are formed that cannot help in the production of miRNA, which can cause cells to grow into tumors. The risk of tumors is mainly increased in the lungs, kidneys, ovaries, and thyroid. Dicer1 Syndrome is transferred in an autosomal dominant pattern. The top treatment is surgery to remove the tumor. References
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Justin Woodard, Sam Hayes, Michal Harel, Ann Taylor, Wally Novak, Alexander Berchansky
