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Dicer1  -  dicer 1, ribonuclease type III

Mus musculus

Synonyms: 1110006F08Rik, D12Ertd7e, Dicer, Double-strand-specific ribonuclease mDCR-1, Endoribonuclease Dicer, ...
 
 
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Disease relevance of Dicer1

  • Anti-Su autoantibodies from both human patients with rheumatic diseases and a mouse model of autoimmunity recognize the endonucleolytic Argonaute and Dicer proteins, both crucial enzymes of the RNAi pathway [1].
 

Psychiatry related information on Dicer1

 

High impact information on Dicer1

  • To address the biological function of RNA interference (RNAi)-related pathways in mammals, we disrupted the gene Dicer1 in mice [3].
  • Loss of Dicer1 lead to lethality early in development, with Dicer1-null embryos depleted of stem cells [3].
  • Mouse oocytes lacking Dicer arrest in meiosis I with multiple disorganized spindles and severe chromosome congression defects [4].
  • Our studies identify Dicer as central to a regulatory network that controls oocyte gene expression programs and that promotes genomic integrity in a cell type notoriously susceptible to aneuploidy [4].
  • Probing the consequences of tissue-restricted Dicer loss in mice indicates a critical role for Dicer during meiosis in the female germline [4].
 

Biological context of Dicer1

  • To elucidate the roles of Dicer1 and the microRNA pathway in early embryo development, we initially evaluated its gene expression in mouse oocytes and embryos in vitro [5].
  • To address the function of RNA interference (RNAi) in transcriptional silencing in mammals, we analyzed genomic imprinting in Dicer1-hypomorphic mice, in which Dicer1 expression was significantly reduced [6].
  • Dicer is the enzyme that cleaves double-stranded RNA (dsRNA) into 21-25-nt-long species responsible for sequence-specific RNA-induced gene silencing at the transcriptional, post-transcriptional, or translational level [7].
  • Re-expression of Dicer in the knockout cells rescued these phenotypes [7].
  • The ribonuclease III enzyme Dicer is essential for the processing of micro-RNAs (miRNAs) and small interfering RNAs (siRNAs) from double-stranded RNA precursors. miRNAs and siRNAs regulate chromatin structure, gene transcription, mRNA stability, and translation in a wide range of organisms [8].
 

Anatomical context of Dicer1

 

Associations of Dicer1 with chemical compounds

  • NMDA stimulation of hippocampal slices, or calcium treatment of synaptoneurosomes, caused a 75 kDa dicer fragment to appear in a calpain-dependent manner [2].
 

Regulatory relationships of Dicer1

 

Other interactions of Dicer1

  • The aberrant Fgf10 expression may contribute to the Dicer morphological defects [10].
  • RNAi induction and activation in mammalian muscle cells where Dicer and eIF2C translation initiation factors are barely expressed [12].
  • T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer [8].
  • The chimeric pRNA complex was found to be processed into functional double-stranded siRNA by Dicer (RNA-specific endonuclease) [13].
 

Analytical, diagnostic and therapeutic context of Dicer1

  • We disrupted the dicer-1 (dcr-1) gene in mouse embryonic stem (ES) cells by conditional gene targeting and generated Dicer-null ES cells [7].
  • Immunoprecipitation experiments suggest that, in human and mouse cells, complex formation occurs between Dicer and eIF2C1 or 2 and that the PIWI domain of eIF2C is essential for the formation of this complex [14].

References

  1. The RNA interference pathway: a new target for autoimmunity. Pruijn, G.J. Arthritis Res. Ther. (2006) [Pubmed]
  2. Dicer and eIF2c are enriched at postsynaptic densities in adult mouse brain and are modified by neuronal activity in a calpain-dependent manner. Lugli, G., Larson, J., Martone, M.E., Jones, Y., Smalheiser, N.R. J. Neurochem. (2005) [Pubmed]
  3. Dicer is essential for mouse development. Bernstein, E., Kim, S.Y., Carmell, M.A., Murchison, E.P., Alcorn, H., Li, M.Z., Mills, A.A., Elledge, S.J., Anderson, K.V., Hannon, G.J. Nat. Genet. (2003) [Pubmed]
  4. Critical roles for Dicer in the female germline. Murchison, E.P., Stein, P., Xuan, Z., Pan, H., Zhang, M.Q., Schultz, R.M., Hannon, G.J. Genes Dev. (2007) [Pubmed]
  5. Dicer1 expression in preimplantation mouse embryos: Involvement of Oct3/4 transcription at the blastocyst stage. Cui, X.S., Shen, X.H., Kim, N.H. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  6. Genomic imprinting in Dicer1-hypomorphic mice. Fukasawa, M., Morita, S., Kimura, M., Horii, T., Ochiya, T., Hatada, I. Cytogenet. Genome Res. (2006) [Pubmed]
  7. Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Kanellopoulou, C., Muljo, S.A., Kung, A.L., Ganesan, S., Drapkin, R., Jenuwein, T., Livingston, D.M., Rajewsky, K. Genes Dev. (2005) [Pubmed]
  8. T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer. Cobb, B.S., Nesterova, T.B., Thompson, E., Hertweck, A., O'Connor, E., Godwin, J., Wilson, C.B., Brockdorff, N., Fisher, A.G., Smale, S.T., Merkenschlager, M. J. Exp. Med. (2005) [Pubmed]
  9. Aberrant T cell differentiation in the absence of Dicer. Muljo, S.A., Ansel, K.M., Kanellopoulou, C., Livingston, D.M., Rao, A., Rajewsky, K. J. Exp. Med. (2005) [Pubmed]
  10. Dicer function is essential for lung epithelium morphogenesis. Harris, K.S., Zhang, Z., McManus, M.T., Harfe, B.D., Sun, X. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Harfe, B.D., McManus, M.T., Mansfield, J.H., Hornstein, E., Tabin, C.J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  12. RNAi induction and activation in mammalian muscle cells where Dicer and eIF2C translation initiation factors are barely expressed. Sago, N., Omi, K., Tamura, Y., Kunugi, H., Toyo-oka, T., Tokunaga, K., Hohjoh, H. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  13. Specific delivery of therapeutic RNAs to cancer cells via the dimerization mechanism of phi29 motor pRNA. Guo, S., Tschammer, N., Mohammed, S., Guo, P. Hum. Gene Ther. (2005) [Pubmed]
  14. Short-interfering-RNA-mediated gene silencing in mammalian cells requires Dicer and eIF2C translation initiation factors. Doi, N., Zenno, S., Ueda, R., Ohki-Hamazaki, H., Ui-Tei, K., Saigo, K. Curr. Biol. (2003) [Pubmed]
 
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