Dicer

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One molecule of the Dicer protein from Giardia intestinalis, which catalyzes the cleavage of dsRNA to siRNAs. The RNase III domains are colored green, the PAZ domain yellow, the platform domain red, and the connector helix blue. The distance between the RNase III and PAZ domains, determined by the length and angle of the connector helix, has been suggested as the determinant for the length of siRNA molecules produced by a given Dicer variant.[1]

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 about 20-25 base pairs long, 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 influences 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.[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 found that the same fundamental mutation in the DICER gene showed up as the common process underlying all of the different cancers they had examined. The DICER gene regulates the development and behavior of normal cells in the body; the mutation of this gene causes its regulating ability to be warped, producing cancerous cells. [4]

History

Dicer was given its name by Emily Bernstein, a 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]

References

  1. ↑ 1.0 1.1 Macrae I, Zhou K, Li F, Repic A, Brooks A, Cande W, Adams P, Doudna J (2006). "Structural basis for double-stranded RNA processing by Dicer". Science 311 (5758): 195–8. doi:10.1126/science.1121638. PMID 16410517. 
  2. ↑ Cenik ES, ..., Zamore PD (2011). "Phosphate and R2D2 restrict the substrate specificity of Dicer-2, an ATP-driven ribonuclease". Molecular Cell 42 (2): 172–84. doi:10.1016/j.molcel.2011.03.002. PMID 21419681. 
  3. ↑ Slack FJ and Weidhaas JB. MicroRNA in cancer prognosis. New England Journal of Medicine 359 (25):2720-2722
  4. ↑ University of British Columbia. "Single gene links rare and unrelated cancers". Medical Xpress. http://medicalxpress.com/news/2011-12-gene-links-rare-unrelated-cancers.html
  5. ↑ Bernstein E, Caudy A, Hammond S, Hannon G (2001). "Role for a bidentate ribonuclease in the initiation step of RNA interference". Nature 409 (6818): 363–6. doi:10.1038/35053110. PMID 11201747. 
  6. ↑ B. Khraiwesh, M.A. Arif, G.I. Seumel, S. Ossowski, D. Weigel, R. Reski , W. Frank (2010) Transcriptional Control of Gene Expression by MicroRNAs" Cell 140,111-122.doi:10.1016/j.cell.2009.12.023
  7. ↑ Discovery: microRNAs can directly turn off genes

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