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Concept
Dicer
Summary
Dicer, also known as endoribonuclease Dicer or helicase with RNase motif, is an enzyme that in humans is encoded by the gene. Being part of the RNase III family, Dicer cleaves double-stranded RNA (dsRNA) and pre-microRNA (pre-miRNA) into short double-stranded RNA fragments called small interfering RNA and microRNA, respectively. These fragments are approximately 20–25 base pairs long with a two-base overhang on the 3′-end. Dicer facilitates the activation of the RNA-induced silencing complex (RISC), which is essential for RNA interference. RISC has a catalytic component Argonaute, which is an endonuclease capable of degrading messenger RNA (mRNA).
Dicer was given its name in 2001 by Stony Brook PhD student Emily Bernstein while conducting research in Gregory Hannon's lab at Cold Spring Harbor Laboratory. Bernstein sought to discover the enzyme responsible for generating small RNA fragments from double-stranded RNA. Dicer's ability to generate around 22 nucleotide RNA fragments was discovered by separating it from the RISC enzyme complex after initiating the RNAi pathway with dsRNA transfection. This experiment showed that RISC was not responsible for generating the observable small nucleotide fragments. Subsequent experiments testing RNase III family enzymes abilities to create RNA fragments narrowed the search to Drosophila CG4792, now named Dicer.
Dicer orthologs are present in many other organisms. 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.
In terms of crystal structure, the first Dicer to be explored was that from the protozoan Giardia intestinalis. The work was done by Ian MacRae while conducting research as a postdoctoral fellow in Jennifer Doudna's lab at the University of California, Berkeley. A PAZ domain and two RNase III domains were discovered by X-ray crystallography.
Official source
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