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Gene Review

Dcr-1  -  Dicer-1

Drosophila melanogaster

Synonyms: CG4792, DCR-1, DCR1, DICER, Dcr, ...
 
 
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Disease relevance of Dcr-1

  • To address the broader role for miRNAs in neuroprotection, we also showed that loss of all miRNAs, by dicer mutation, dramatically enhances pathogenic polyQ protein toxicity in flies and in human HeLa cells [1].
 

High impact information on Dcr-1

  • The requirement for Dicer in the instability of ARE-containing mRNA (ARE-RNA) was confirmed in HeLa cells [2].
  • Mutation in dicer-1 blocks processing of miRNA precursors, whereas dicer-2 mutants are defective for processing siRNA precursors [3].
  • The pathway of RNA interference starts when Dicer cuts dsRNA into small interfering RNAs (siRNAs) that subsequently target homologous mRNAs for destruction. microRNA processing from stem loop precursors similarly requires Dicer activity [4].
  • Both pathways require the RNA-processing enzyme Dicer to produce the active small-RNA component that represses gene expression [5].
  • Therefore, R3D1-L functions in concert with Dicer-1 in miRNA biogenesis and is required for reproductive development in Drosophila [6].
 

Biological context of Dcr-1

  • The association of AGO1 with Dicer-1 and pre-miRNA also suggests that AGO1 is involved in miRNA biogenesis [7].
  • Here we show that Drosophila Dicer-1 interacts with Loquacious, a double-stranded RNA-binding domain protein [8].
  • During RNA interference (RNAi), Dicer generates short interfering RNAs (siRNAs), which then guide target mRNA cleavage by the RISC complex [9].
  • PAZ can bind the characteristic two-base 3' overhangs of siRNAs, indicating that although PAZ may not be a primary nucleic acid binding site in Dicer or RISC, it may contribute to the specific and productive incorporation of siRNAs and miRNAs into the RNAi pathway [10].
  • New data show that Dicer-1 also requires a double-stranded RNA binding protein called Loquacious for efficient microRNA-mediated gene silencing [11].
 

Anatomical context of Dcr-1

  • Dcr-1 maintains Drosophila ovarian stem cells [12].
  • In Drosophila, repeat-associated small interfering RNAs (rasiRNAs) are produced in the germ line by a Dicer-independent pathway and function through the PIWI subfamily of Argonautes to ensure silencing of retrotransposons [13].
  • To identify the global range of miRNA-regulated genes during oocyte maturation of Drosophila, we compared the proteome from wild-type oocytes with the proteome from oocytes lacking the dicer-1 gene, which is essential for biogenesis of miRNAs [14].
 

Regulatory relationships of Dcr-1

  • While depletion of R3D1-L by RNAi causes accumulation of precursor miRNA (pre-miRNA) in S2 cells, recombinant R3D1-L enhances miRNA production by Dicer-1 in vitro [6].
 

Other interactions of Dcr-1

References

  1. A new role for microRNA pathways: modulation of degeneration induced by pathogenic human disease proteins. Bilen, J., Liu, N., Bonini, N.M. Cell Cycle (2006) [Pubmed]
  2. Involvement of microRNA in AU-rich element-mediated mRNA instability. Jing, Q., Huang, S., Guth, S., Zarubin, T., Motoyama, A., Chen, J., Di Padova, F., Lin, S.C., Gram, H., Han, J. Cell (2005) [Pubmed]
  3. Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways. Lee, Y.S., Nakahara, K., Pham, J.W., Kim, K., He, Z., Sontheimer, E.J., Carthew, R.W. Cell (2004) [Pubmed]
  4. Dicers at RISC; the mechanism of RNAi. Tijsterman, M., Plasterk, R.H. Cell (2004) [Pubmed]
  5. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Hutvágner, G., McLachlan, J., Pasquinelli, A.E., Bálint, E., Tuschl, T., Zamore, P.D. Science (2001) [Pubmed]
  6. Dicer-1 and R3D1-L catalyze microRNA maturation in Drosophila. Jiang, F., Ye, X., Liu, X., Fincher, L., McKearin, D., Liu, Q. Genes Dev. (2005) [Pubmed]
  7. Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways. Okamura, K., Ishizuka, A., Siomi, H., Siomi, M.C. Genes Dev. (2004) [Pubmed]
  8. Processing of pre-microRNAs by the Dicer-1-Loquacious complex in Drosophila cells. Saito, K., Ishizuka, A., Siomi, H., Siomi, M.C. PLoS Biol. (2005) [Pubmed]
  9. R2D2 leads the silencing trigger to mRNA's death star. Pellino, J.L., Sontheimer, E.J. Cell (2003) [Pubmed]
  10. The crystal structure of the Argonaute2 PAZ domain reveals an RNA binding motif in RNAi effector complexes. Song, J.J., Liu, J., Tolia, N.H., Schneiderman, J., Smith, S.K., Martienssen, R.A., Hannon, G.J., Joshua-Tor, L. Nat. Struct. Biol. (2003) [Pubmed]
  11. MicroRNAs: Loquacious speaks out. Leuschner, P.J., Obernosterer, G., Martinez, J. Curr. Biol. (2005) [Pubmed]
  12. Dcr-1 maintains Drosophila ovarian stem cells. Jin, Z., Xie, T. Curr. Biol. (2007) [Pubmed]
  13. A slicer-mediated mechanism for repeat-associated siRNA 5' end formation in Drosophila. Gunawardane, L.S., Saito, K., Nishida, K.M., Miyoshi, K., Kawamura, Y., Nagami, T., Siomi, H., Siomi, M.C. Science (2007) [Pubmed]
  14. Targets of microRNA regulation in the Drosophila oocyte proteome. Nakahara, K., Kim, K., Sciulli, C., Dowd, S.R., Minden, J.S., Carthew, R.W. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  15. Normal microRNA maturation and germ-line stem cell maintenance requires Loquacious, a double-stranded RNA-binding domain protein. Förstemann, K., Tomari, Y., Du, T., Vagin, V.V., Denli, A.M., Bratu, D.P., Klattenhoff, C., Theurkauf, W.E., Zamore, P.D. PLoS Biol. (2005) [Pubmed]
 
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