The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

DICER1  -  dicer 1, ribonuclease type III

Homo sapiens

Synonyms: DCR1, DICER, Dicer, Dicer1e, Endoribonuclease Dicer, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of DICER1


High impact information on DICER1

  • While Dicer, which produces small interfering RNAs, is currently the focus of intense interest, the structurally simpler bacterial RNase III serves as a paradigm for the entire family [6].
  • Here we show that RISC is composed of Dicer, the double-stranded RNA binding protein TRBP, and Argonaute2 [7].
  • Dicer is a multidomain ribonuclease that processes double-stranded RNAs (dsRNAs) to 21 nt small interfering RNAs (siRNAs) during RNA interference, and excises microRNAs from precursor hairpins [2].
  • Based on these and other data, we propose that Dicer functions through intramolecular dimerization of its two RNase III domains, assisted by the flanking RNA binding domains, PAZ and dsRBD [2].
  • At an early step in RNAi, an RNaseIII-related enzyme, Dicer (DCR-1), processes long-trigger dsRNA into small interfering RNAs (siRNAs) [8].

Biological context of DICER1


Anatomical context of DICER1

  • We postulate that at least some members of the human Argonaute family may be involved in the development and maintenance of stem cells through the RNA-mediated gene-quelling mechanisms associated with DICER [12].
  • We generated HEK293 cell lines depleted of Dicer or individual Ago proteins [10].
  • Human Dicer expressed in mammalian cells colocalized with calreticulin, a resident protein of the endoplasmic reticulum [13].
  • Our results suggest that Dicer is essential for turnover of a substantial subset of maternal transcripts that are normally lost during oocyte maturation [14].
  • Dicer facilitates, in a cell-autonomous fashion, the development of T reg cells in the thymus and the efficient induction of Foxp3 by transforming growth factor beta [15].

Associations of DICER1 with chemical compounds

  • However, over the last 2 years, great strides have been made towards elucidating how PPD proteins and Dicer regulate gene-silencing at the pre- and post-transcriptional levels [16].
  • In this study, we demonstrate that siRNAs that have been generated in vitro by recombinant human Dicer (re-hDicer) significantly suppress not only the exogenous expression of a puromycin-resistance gene but also the endogenous expression of H-ras, c-jun and c-fos [17].
  • Incorporation of an RNA aptamer for theophylline in the loop region of a short hairpin RNA (shRNA) designed to silence fluorescent reporter genes led to dose-dependent inhibition of RNAi by theophylline. shRNA cleavage experiments using recombinant Dicer demonstrated that theophylline inhibited cleavage of an aptamer-fused shRNA by Dicer in vitro [18].
  • Specifically, dsRNA is responsible for stimulating important protective responses, such as the activation of dicer-related antiviral pathways, induction of type 1 IFN, and stimulation of dsRNA-activated protein kinase and oligoadenylate synthetase [19].
  • Exp5 binds correctly processed pre-miRNAs directly and specifically, in a Ran guanosine triphosphate-dependent manner, but interacts only weakly with extended pre-miRNAs that yield incorrect miRNAs when processed by Dicer in vitro [20].

Physical interactions of DICER1

  • In vitro reconstitution assays demonstrated that TRBP is required for the recruitment of Ago2 to the small interfering RNA (siRNA) bound by Dicer [4].
  • In this work, we describe the identification of TRBP (human immunodeficiency virus (HIV-1) transactivating response (TAR) RNA-binding protein) as a protein partner of human Dicer [21].
  • Such a study revealed that EB-3 cells possess 4-fold higher expression of Dicer gene coupled with 2-fold higher activity of RNA polymerase III than that observed in normal human lymphocytes. siRNAs derived from EB-3 cells had the inherent capacity to suppress c-myc gene expression in normal cells but not in native cells [22].
  • It has been established that the double stranded short interfering RNAs (siRNAs) originate by the activity of a dsRNA-specific endonuclease, Dicer. siRNA in conjunction with a multiple enzyme complex called RNA-induced silencing complex (RISC) locates to the specific sites on mRNA and degrades it by endonuclease and exonuclease activities [23].

Regulatory relationships of DICER1


Other interactions of DICER1

  • The 3'-untranslated region sequences of a few hundred transcripts that were commonly up-regulated upon Ago2 and Dicer knock-downs showed a significant enrichment of putative miRNA-binding sites [10].
  • TAR RNA-binding protein, TRBP, was recently discovered to be an essential partner for Dicer and a crucial component of the RNA-induced silencing complex (RISC), a critical element of the RNA interference (RNAi) of the cell apparatus [26].
  • Dicer and positive charge of proteins decrease the stability of RNA containing the AU-rich element of GM-CSF [27].
  • Processing of the microRNA let-7 precursor by Dicer produced an apparently mature let-7 RNA [13].
  • Comprehensive phylogenetic analyses of fungal Argonaute, Dicer, and RNA-dependent RNA polymerase-like proteins have been performed to gain insights into the diversification of RNA silencing pathways during the evolution of fungi [28].

Analytical, diagnostic and therapeutic context of DICER1


  1. RNASEN Regulates Cell Proliferation and Affects Survival in Esophageal Cancer Patients. Sugito, N., Ishiguro, H., Kuwabara, Y., Kimura, M., Mitsui, A., Kurehara, H., Ando, T., Mori, R., Takashima, N., Ogawa, R., Fujii, Y. Clin. Cancer Res. (2006) [Pubmed]
  2. Single processing center models for human Dicer and bacterial RNase III. Zhang, H., Kolb, F.A., Jaskiewicz, L., Westhof, E., Filipowicz, W. Cell (2004) [Pubmed]
  3. Up-Regulation of Dicer, a Component of the MicroRNA Machinery, in Prostate Adenocarcinoma. Chiosea, S., Jelezcova, E., Chandran, U., Acquafondata, M., McHale, T., Sobol, R.W., Dhir, R. Am. J. Pathol. (2006) [Pubmed]
  4. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Chendrimada, T.P., Gregory, R.I., Kumaraswamy, E., Norman, J., Cooch, N., Nishikura, K., Shiekhattar, R. Nature (2005) [Pubmed]
  5. Ribonuclease dicer cleaves triplet repeat hairpins into shorter repeats that silence specific targets. Krol, J., Fiszer, A., Mykowska, A., Sobczak, K., de Mezer, M., Krzyzosiak, W.J. Mol. Cell (2007) [Pubmed]
  6. Structural insight into the mechanism of double-stranded RNA processing by ribonuclease III. Gan, J., Tropea, J.E., Austin, B.P., Court, D.L., Waugh, D.S., Ji, X. Cell (2006) [Pubmed]
  7. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Gregory, R.I., Chendrimada, T.P., Cooch, N., Shiekhattar, R. Cell (2005) [Pubmed]
  8. The dsRNA binding protein RDE-4 interacts with RDE-1, DCR-1, and a DExH-box helicase to direct RNAi in C. elegans. Tabara, H., Yigit, E., Siomi, H., Mello, C.C. Cell (2002) [Pubmed]
  9. Translation Repression in Human Cells by MicroRNA-Induced Gene Silencing Requires RCK/p54. Chu, C.Y., Rana, T.M. PLoS Biol. (2006) [Pubmed]
  10. Effects of Dicer and Argonaute down-regulation on mRNA levels in human HEK293 cells. Schmitter, D., Filkowski, J., Sewer, A., Pillai, R.S., Oakeley, E.J., Zavolan, M., Svoboda, P., Filipowicz, W. Nucleic Acids Res. (2006) [Pubmed]
  11. MicroRNA-1 and microRNA-133a expression are decreased during skeletal muscle hypertrophy. McCarthy, J.J., Esser, K.A. J. Appl. Physiol. (2007) [Pubmed]
  12. Identification of eight members of the Argonaute family in the human genome small star, filled. Sasaki, T., Shiohama, A., Minoshima, S., Shimizu, N. Genomics (2003) [Pubmed]
  13. Ribonuclease activity and RNA binding of recombinant human Dicer. Provost, P., Dishart, D., Doucet, J., Frendewey, D., Samuelsson, B., Rådmark, O. EMBO J. (2002) [Pubmed]
  14. 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]
  15. A role for Dicer in immune regulation. Cobb, B.S., Hertweck, A., Smith, J., O'connor, E., Graf, D., Cook, T., Smale, S.T., Sakaguchi, S., Livesey, F.J., Fisher, A.G., Merkenschlager, M. J. Exp. Med. (2006) [Pubmed]
  16. Exploring the functions of RNA interference pathway proteins: some functions are more RISCy than others? Jaronczyk, K., Carmichael, J.B., Hobman, T.C. Biochem. J. (2005) [Pubmed]
  17. siRNAs generated by recombinant human Dicer induce specific and significant but target site-independent gene silencing in human cells. Kawasaki, H., Suyama, E., Iyo, M., Taira, K. Nucleic Acids Res. (2003) [Pubmed]
  18. Artificial control of gene expression in mammalian cells by modulating RNA interference through aptamer-small molecule interaction. An, C.I., Trinh, V.B., Yokobayashi, Y. RNA (2006) [Pubmed]
  19. Immune responses to dsRNA: implications for gene silencing technologies. Karpala, A.J., Doran, T.J., Bean, A.G. Immunol. Cell Biol. (2005) [Pubmed]
  20. Nuclear export of microRNA precursors. Lund, E., Güttinger, S., Calado, A., Dahlberg, J.E., Kutay, U. Science (2004) [Pubmed]
  21. TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing. Haase, A.D., Jaskiewicz, L., Zhang, H., Lainé, S., Sack, R., Gatignol, A., Filipowicz, W. EMBO Rep. (2005) [Pubmed]
  22. Defective RNA-mediated c-myc gene silencing pathway in Burkitt's lymphoma. Kaul, D., Sikand, K. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  23. Know-how of RNA interference and its applications in research and therapy. Wadhwa, R., Kaul, S.C., Miyagishi, M., Taira, K. Mutat. Res. (2004) [Pubmed]
  24. Characterization of the interactions between mammalian PAZ PIWI domain proteins and Dicer. Tahbaz, N., Kolb, F.A., Zhang, H., Jaronczyk, K., Filipowicz, W., Hobman, T.C. EMBO Rep. (2004) [Pubmed]
  25. Dicer-dependent turnover of intergenic transcripts from the human beta-globin gene cluster. Haussecker, D., Proudfoot, N.J. Mol. Cell. Biol. (2005) [Pubmed]
  26. HIV-1 TAR RNA Subverts RNA Interference in Transfected Cells through Sequestration of TAR RNA-binding Protein, TRBP. Bennasser, Y., Yeung, M.L., Jeang, K.T. J. Biol. Chem. (2006) [Pubmed]
  27. Dicer and positive charge of proteins decrease the stability of RNA containing the AU-rich element of GM-CSF. Takahashi, H., Maeda, M., Sawa, H., Hasegawa, H., Moriyama, M., Sata, T., Hall, W.W., Kurata, T. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  28. Evolution and diversification of RNA silencing proteins in fungi. Nakayashiki, H., Kadotani, N., Mayama, S. J. Mol. Evol. (2006) [Pubmed]
  29. Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase. Matsuda, S., Ichigotani, Y., Okuda, T., Irimura, T., Nakatsugawa, S., Hamaguchi, M. Biochim. Biophys. Acta (2000) [Pubmed]
  30. Functional polarity is introduced by Dicer processing of short substrate RNAs. Rose, S.D., Kim, D.H., Amarzguioui, M., Heidel, J.D., Collingwood, M.A., Davis, M.E., Rossi, J.J., Behlke, M.A. Nucleic Acids Res. (2005) [Pubmed]
  31. Crystallization and preliminary X-ray analysis of the C-terminal RNase III domain of human Dicer. Takeshita, D., Zenno, S., Lee, W.C., Nagata, K., Saigo, K., Tanokura, M. Acta Crystallograph. Sect. F Struct. Biol. Cryst. Commun. (2006) [Pubmed]
WikiGenes - Universities