Dicer1

Summary

Gene Symbol: Dicer1
Description: dicer 1 ribonuclease III
Alias: endoribonuclease Dicer, Dicer1, Dcr-1 homolog, dicer 1, ribonuclease type III
Species: rat
Products:     Dicer1

Top Publications

  1. Maniataki E, Mourelatos Z. A human, ATP-independent, RISC assembly machine fueled by pre-miRNA. Genes Dev. 2005;19:2979-90 pubmed
    ..We suggest that the miRLC couples the processing of the pre-miRNA substrate to the unwinding of the product and that after loading of the mature miRNA to Ago2, the miRLC disassembles and the miRNP is released. ..
  2. Kok K, Ng M, Ching Y, Jin D. Human TRBP and PACT directly interact with each other and associate with dicer to facilitate the production of small interfering RNA. J Biol Chem. 2007;282:17649-57 pubmed
    ..Our work significantly alters the current model for the assembly and function of the Dicer-containing complex that generates siRNA and micro-RNA in human. ..
  3. Wang H, Noland C, Siridechadilok B, Taylor D, Ma E, Felderer K, et al. Structural insights into RNA processing by the human RISC-loading complex. Nat Struct Mol Biol. 2009;16:1148-53 pubmed publisher
    ..A model generated by docking the available atomic structures of Dicer and Argonaute homologs into the RLC reconstruction suggests a mechanism for siRNA transfer from Dicer to AGO2. ..
  4. Ma E, Macrae I, Kirsch J, Doudna J. Autoinhibition of human dicer by its internal helicase domain. J Mol Biol. 2008;380:237-43 pubmed publisher
    ..These results suggest that the DExD/H-box domain likely disrupts the functionality of the Dicer active site until a structural rearrangement occurs, perhaps upon assembly with its molecular partners. ..
  5. Macrae I, Ma E, Zhou M, Robinson C, Doudna J. In vitro reconstitution of the human RISC-loading complex. Proc Natl Acad Sci U S A. 2008;105:512-7 pubmed publisher
    ..Furthermore, once Ago2 is loaded with an miRNA, it tends to dissociate from the rest of the complex. These results lay the groundwork for future structural and functional dissection of RISC loading in humans. ..
  6. Yi R, O Carroll D, Pasolli H, Zhang Z, Dietrich F, Tarakhovsky A, et al. Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs. Nat Genet. 2006;38:356-62 pubmed
    ..To explore the functional significance of this finding, we conditionally targeted Dicer1 gene ablation in embryonic skin progenitors...
  7. Harris K, Zhang Z, McManus M, Harfe B, Sun X. Dicer function is essential for lung epithelium morphogenesis. Proc Natl Acad Sci U S A. 2006;103:2208-13 pubmed
    ..The aberrant Fgf10 expression may contribute to the Dicer morphological defects. However, the mechanism by which DICER functions in the epithelium to influence Fgf10 expression in the mesenchyme remains unknown. ..
  8. Chendrimada T, Gregory R, Kumaraswamy E, Norman J, Cooch N, Nishikura K, et al. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature. 2005;436:740-4 pubmed
    ..These results support a role of the Dicer-TRBP complex not only in miRNA processing but also as a platform for RISC assembly. ..
  9. Hutvagner G, McLachlan J, Pasquinelli A, Balint E, Tuschl T, Zamore P. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science. 2001;293:834-8 pubmed
    ..Thus, the RNA interference and stRNA pathways intersect. Both pathways require the RNA-processing enzyme Dicer to produce the active small-RNA component that represses gene expression. ..

More Information

Publications57

  1. Hayashi K, Chuva de Sousa Lopes S, Kaneda M, Tang F, Hajkova P, Lao K, et al. MicroRNA biogenesis is required for mouse primordial germ cell development and spermatogenesis. PLoS ONE. 2008;3:e1738 pubmed publisher
    ..Furthermore, based on normal spermatogenesis in Argonaute2-deficient testis, the critical function of Dicer in spermatogenesis is independent of Argonaute2. ..
  2. Zhang H, Kolb F, Brondani V, Billy E, Filipowicz W. Human Dicer preferentially cleaves dsRNAs at their termini without a requirement for ATP. EMBO J. 2002;21:5875-85 pubmed
    ..Additional experiments suggest that if ATP participates in the Dicer reaction in mammalian cells, it might be involved in product release needed for the multiple turnover of the enzyme. ..
  3. Liu X, Jin D, McManus M, Mourelatos Z. Precursor microRNA-programmed silencing complex assembly pathways in mammals. Mol Cell. 2012;46:507-17 pubmed publisher
    ..Our studies provide a comprehensive view of miRNP/RISC assembly pathways in mammals, and our assay provides a versatile platform for further mechanistic dissection of such pathways in mammals. ..
  4. Lynn F, Skewes Cox P, Kosaka Y, McManus M, Harfe B, German M. MicroRNA expression is required for pancreatic islet cell genesis in the mouse. Diabetes. 2007;56:2938-45 pubmed
    ..To assess the overall contribution of miRNAs to pancreatic development, Dicer1, an enzyme required for miRNA processing, was conditionally deleted from the developing pancreas...
  5. Kanellopoulou C, Muljo S, Kung A, Ganesan S, Drapkin R, Jenuwein T, et al. Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev. 2005;19:489-501 pubmed
  6. Harfe B, McManus M, Mansfield J, Hornstein E, Tabin C. The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc Natl Acad Sci U S A. 2005;102:10898-903 pubmed
    ..Thus, Dicer is required for the formation of normal mouse limbs. Strikingly, however, we did not detect defects in basic patterning or in tissue-specific differentiation of Dicer-deficient limb buds. ..
  7. Bernstein E, Kim S, Carmell M, Murchison E, Alcorn H, Li M, et al. Dicer is essential for mouse development. Nat Genet. 2003;35:215-7 pubmed
    To address the biological function of RNA interference (RNAi)-related pathways in mammals, we disrupted the gene Dicer1 in mice. Loss of Dicer1 lead to lethality early in development, with Dicer1-null embryos depleted of stem cells...
  8. Yang W, Yang D, Na S, Sandusky G, Zhang Q, Zhao G. Dicer is required for embryonic angiogenesis during mouse development. J Biol Chem. 2005;280:9330-5 pubmed
  9. Bernstein E, Caudy A, Hammond S, Hannon G. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001;409:363-6 pubmed
    ..The enzyme has a distinctive structure, which includes a helicase domain and dual RNase III motifs. Dicer also contains a region of homology to the RDE1/QDE2/ARGONAUTE family that has been genetically linked to RNAi. ..
  10. Park J, Heo I, Tian Y, Simanshu D, Chang H, Jee D, et al. Dicer recognizes the 5' end of RNA for efficient and accurate processing. Nature. 2011;475:201-5 pubmed publisher
    ..Thus, 5'-end recognition by Dicer is important for precise and effective biogenesis of miRNAs. Insights from this study should also afford practical benefits to the design of small hairpin RNAs. ..
  11. Björkgren I, Saastamoinen L, Krutskikh A, Huhtaniemi I, Poutanen M, Sipila P. Dicer1 ablation in the mouse epididymis causes dedifferentiation of the epithelium and imbalance in sex steroid signaling. PLoS ONE. 2012;7:e38457 pubmed publisher
    ..By utilizing the Cre-LoxP system we have generated a conditional knock-out of Dicer1 in the two most proximal segments of the mouse epididymis...
  12. Hornstein E, Mansfield J, Yekta S, Hu J, Harfe B, McManus M, et al. The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development. Nature. 2005;438:671-4 pubmed
  13. Zheng G, Ravi A, Calabrese J, Medeiros L, Kirak O, Dennis L, et al. A latent pro-survival function for the mir-290-295 cluster in mouse embryonic stem cells. PLoS Genet. 2011;7:e1002054 pubmed publisher
    ..Similarly, this cluster may mediate chemotherapeutic resistance in a neoplastic context, making it a useful clinical target. ..
  14. Otsuka M, Jing Q, Georgel P, New L, Chen J, Mols J, et al. Hypersusceptibility to vesicular stomatitis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression. Immunity. 2007;27:123-34 pubmed
    ..We show that because of impaired miRNA production, mice with a variant Dicer1 allele (Dicer1(d/d)) were more susceptible to vesicular stomatitis virus (VSV) infection...
  15. Kim B, Woo J, Kanellopoulou C, Shivdasani R. Regulation of mouse stomach development and Barx1 expression by specific microRNAs. Development. 2011;138:1081-6 pubmed publisher
    ..These results indicate that miRNAs are required for proper digestive tract organogenesis and that miR-7a and miR-203 control expression of the stomach homeotic regulator Barx1. ..
  16. Friedman L, Dror A, Mor E, Tenne T, Toren G, Satoh T, et al. MicroRNAs are essential for development and function of inner ear hair cells in vertebrates. Proc Natl Acad Sci U S A. 2009;106:7915-20 pubmed publisher
    ..A conditional knock-out mouse for Dicer1 demonstrated that miRNAs are crucial for postnatal survival of functional hair cells of the inner ear...
  17. Frederikse P, Donnelly R, Partyka L. miRNA and Dicer in the mammalian lens: expression of brain-specific miRNAs in the lens. Histochem Cell Biol. 2006;126:1-8 pubmed
  18. Chen J, Huang Y, Mazzoni E, Tan G, Zavadil J, Wichterle H. Mir-17-3p controls spinal neural progenitor patterning by regulating Olig2/Irx3 cross-repressive loop. Neuron. 2011;69:721-35 pubmed publisher
  19. Hanina S, Mifsud W, Down T, Hayashi K, O Carroll D, Lao K, et al. Genome-wide identification of targets and function of individual MicroRNAs in mouse embryonic stem cells. PLoS Genet. 2010;6:e1001163 pubmed publisher
    ..To identify miR-294 targets, we used Dicer1-null ES cells, which lack all endogenous mature miRNAs, and introduced just miR-294 into these ES cells...
  20. Michon F, Tummers M, Kyyrönen M, Frilander M, Thesleff I. Tooth morphogenesis and ameloblast differentiation are regulated by micro-RNAs. Dev Biol. 2010;340:355-68 pubmed publisher
    ..Based on our findings we suggest that miRNAs modulate tooth morphogenesis largely by fine tuning conserved signaling networks and that miRNAs may have played important roles during tooth evolution...
  21. Kim B, Choi M. Non-canonical microRNAs miR-320 and miR-702 promote proliferation in Dgcr8-deficient embryonic stem cells. Biochem Biophys Res Commun. 2012;426:183-9 pubmed publisher
    ..This is accomplished by targeting the 3'-untranslated regions of the cell cycle inhibitors p57 and p21 and thereby inhibiting their expression. This is the first report of the crucial role of non-canonical microRNAs in ESCs. ..
  22. Huang V, Place R, Portnoy V, Wang J, Qi Z, Jia Z, et al. Upregulation of Cyclin B1 by miRNA and its implications in cancer. Nucleic Acids Res. 2012;40:1695-707 pubmed publisher
    ..Such phenotypes were recapitulated by overexpression of Ccnb1. Our findings reveal an endogenous system by which miRNA functions to activate Ccnb1 expression in mouse cells and manipulate in vivo tumor development/growth. ..
  23. Liu Z, Wang J, Li G, Wang H. Structure of precursor microRNA's terminal loop regulates human Dicer's dicing activity by switching DExH/D domain. Protein Cell. 2015;6:185-93 pubmed publisher
  24. Chong M, Rasmussen J, Rudensky A, Rundensky A, Littman D. The RNAseIII enzyme Drosha is critical in T cells for preventing lethal inflammatory disease. J Exp Med. 2008;205:2005-17 pubmed publisher
    ..Thus, miRNA-dependent regulation is critical for preventing spontaneous inflammation and autoimmunity. ..
  25. Chen J, Murchison E, Tang R, Callis T, Tatsuguchi M, Deng Z, et al. Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure. Proc Natl Acad Sci U S A. 2008;105:2111-6 pubmed publisher
    ..Together, our studies demonstrate essential roles for Dicer in cardiac contraction and indicate that miRNAs play critical roles in normal cardiac function and under pathological conditions. ..
  26. Beltrami C, Besnier M, Shantikumar S, Shearn A, Rajakaruna C, Laftah A, et al. Human Pericardial Fluid Contains Exosomes Enriched with Cardiovascular-Expressed MicroRNAs and Promotes Therapeutic Angiogenesis. Mol Ther. 2017;25:679-693 pubmed publisher
    ..Collectively, our data support the concept that PF exosomes orchestrate vascular repair via miRNA transfer. ..
  27. Li Y, Mao L, Gao Y, Baral S, Zhou Y, Hu B. MicroRNA-107 contributes to post-stroke angiogenesis by targeting Dicer-1. Sci Rep. 2015;5:13316 pubmed publisher
    ..This process might be a protective mechanism for ischemia-induced cerebral injury and miR-107 might be used as a novel tool in stroke treatment. ..
  28. De Pietri Tonelli D, Pulvers J, Haffner C, Murchison E, Hannon G, Huttner W. miRNAs are essential for survival and differentiation of newborn neurons but not for expansion of neural progenitors during early neurogenesis in the mouse embryonic neocortex. Development. 2008;135:3911-21 pubmed publisher
    ..5. Our results support the emerging concept that progenitors are less dependent on miRNAs than their differentiated progeny, and raise interesting perspectives as to the expansion of somatic stem cells. ..
  29. Barbato C, Ciotti M, Serafino A, Calissano P, Cogoni C. Dicer expression and localization in post-mitotic neurons. Brain Res. 2007;1175:17-27 pubmed
  30. Robb G, Rana T. RNA helicase A interacts with RISC in human cells and functions in RISC loading. Mol Cell. 2007;26:523-37 pubmed
    ..Our results identify RHA as a RISC component and demonstrate that RHA functions in RISC as an siRNA-loading factor. ..
  31. Flemr M, Malik R, Franke V, Nejepinska J, Sedlacek R, Vlahovicek K, et al. A retrotransposon-driven dicer isoform directs endogenous small interfering RNA production in mouse oocytes. Cell. 2013;155:807-16 pubmed publisher
    ..The alternative Dicer isoform, whose phylogenetic origin demonstrates evolutionary plasticity of RNA-silencing pathways, is the main determinant of endogenous RNAi activity in the mouse female germline. ..
  32. Maida Y, Yasukawa M, Furuuchi M, Lassmann T, Possemato R, Okamoto N, et al. An RNA-dependent RNA polymerase formed by TERT and the RMRP RNA. Nature. 2009;461:230-5 pubmed publisher
    ..RdRP) activity and produces double-stranded RNAs that can be processed into small interfering RNA in a Dicer (also known as DICER1)-dependent manner. These observations identify a mammalian RdRP composed of TERT in complex with RMRP.
  33. Provost P, Dishart D, Doucet J, Frendewey D, Samuelsson B, Radmark O. Ribonuclease activity and RNA binding of recombinant human Dicer. EMBO J. 2002;21:5864-74 pubmed
    ..Availability of the recombinant Dicer protein will help improve our understanding of RNA silencing and other Dicer-related processes. ..
  34. Ungvari Z, Tucsek Z, Sosnowska D, Toth P, Gautam T, Podlutsky A, et al. Aging-induced dysregulation of dicer1-dependent microRNA expression impairs angiogenic capacity of rat cerebromicrovascular endothelial cells. J Gerontol A Biol Sci Med Sci. 2013;68:877-91 pubmed publisher
    ..To test the hypothesis that dysregulation of Dicer1 (ribonuclease III, a key enzyme of the microRNA [miRNA] machinery) impairs endothelial angiogenic capacity in ..
  35. Kim J, Inoue K, Ishii J, Vanti W, Voronov S, Murchison E, et al. A MicroRNA feedback circuit in midbrain dopamine neurons. Science. 2007;317:1220-4 pubmed
    ..We propose a role for this feedback circuit in the fine-tuning of dopaminergic behaviors such as locomotion. ..
  36. Pichu S, Krishnamoorthy S, Zhang B, Jing Y, Shishkov A, Ponnappa B. Dicer-substrate siRNA inhibits tumor necrosis factor alpha secretion in Kupffer cells in vitro: in vivo targeting of Kupffer cells by siRNA-liposomes. Pharmacol Res. 2012;65:48-55 pubmed publisher
    ..These data demonstrate the identification of a highly efficacious siRNA formulation, which can be used in the treatment of TNF-? mediated diseases. ..
  37. Doi N, Zenno S, Ueda R, Ohki Hamazaki H, Ui Tei K, Saigo K. Short-interfering-RNA-mediated gene silencing in mammalian cells requires Dicer and eIF2C translation initiation factors. Curr Biol. 2003;13:41-6 pubmed
    ..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. ..
  38. Hengst U, Cox L, Macosko E, Jaffrey S. Functional and selective RNA interference in developing axons and growth cones. J Neurosci. 2006;26:5727-32 pubmed
    ..Our results demonstrate functional and potent RNAi in axons and identify an approach to spatially regulate mRNA transcripts at a subcellular level in neurons. ..
  39. Zheng G, Ravi A, Gould G, Burge C, Sharp P. Genome-wide impact of a recently expanded microRNA cluster in mouse. Proc Natl Acad Sci U S A. 2011;108:15804-9 pubmed publisher
  40. Chen W, Zhang Z, Chen J, Zhang J, Zhang J, Wu Y, et al. HCV core protein interacts with Dicer to antagonize RNA silencing. Virus Res. 2008;133:250-8 pubmed publisher
    ..This anti-Dicer ability of core protein may contribute to the persistent viral infection and pathogenesis of HCV. ..
  41. Sheehy N, Cordes K, White M, Ivey K, Srivastava D. The neural crest-enriched microRNA miR-452 regulates epithelial-mesenchymal signaling in the first pharyngeal arch. Development. 2010;137:4307-16 pubmed publisher
    ..These results suggest that post-transcriptional regulation by miRNAs is required for differentiation of NCC-derived tissues and that miR-452 is involved in epithelial-mesenchymal signaling in the pharyngeal arch. ..
  42. Lee H, Zhou K, Smith A, Noland C, Doudna J. Differential roles of human Dicer-binding proteins TRBP and PACT in small RNA processing. Nucleic Acids Res. 2013;41:6568-76 pubmed publisher
    ..These results support the conclusion that in humans, Dicer-associated dsRNA-binding proteins are important regulatory factors that contribute both substrate and cleavage specificity during miRNA and siRNA production. ..
  43. Cheung T, Quach N, Charville G, Liu L, Park L, Edalati A, et al. Maintenance of muscle stem-cell quiescence by microRNA-489. Nature. 2012;482:524-8 pubmed publisher
    ..Our results provide evidence of the miRNA pathway in general, and of a specific miRNA, miR-489, in actively maintaining the quiescent state of an adult stem-cell population. ..
  44. Rybak A, Fuchs H, Smirnova L, Brandt C, Pohl E, Nitsch R, et al. A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment. Nat Cell Biol. 2008;10:987-93 pubmed publisher
  45. Verrier J, Semple Rowland S, Madorsky I, Papin J, Notterpek L. Reduction of Dicer impairs Schwann cell differentiation and myelination. J Neurosci Res. 2010;88:2558-68 pubmed publisher
    ..These findings support a critical role for Dicer and miRNAs in Schwann cell differentiation and myelination. ..
  46. Dugas J, Cuellar T, Scholze A, Ason B, Ibrahim A, Emery B, et al. Dicer1 and miR-219 Are required for normal oligodendrocyte differentiation and myelination. Neuron. 2010;65:597-611 pubmed publisher
    ..mice in which microRNA processing was disrupted in OL precursor cells (OPCs) and OLs by targeted deletion of Dicer1. We found that inhibition of OPC-OL miRNA processing disrupts normal CNS myelination and that OPCs lacking mature ..
  47. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010;11:597-610 pubmed publisher
    ..Such regulation has an important role in the context-specific functions of miRNAs. ..
  48. Pereira J, Baumann R, Norrmen C, Somandin C, Miehe M, Jacob C, et al. Dicer in Schwann cells is required for myelination and axonal integrity. J Neurosci. 2010;30:6763-75 pubmed publisher
    ..Thus, our data indicate that miRNAs critically regulate Schwann cell gene expression that is required for myelination and to maintain axons via axon-glia interactions. ..