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

• A portion of dicer and eIF2c were associated with each other and with fragile X mental retardation protein (FMRP), as assessed by co-immunoprecipitation [2].

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

• Dicer1 expression in preimplantation mouse embryos: Involvement of Oct3/4 transcription at the blastocyst stage [5].
• However, Dicer-deficient CD4(+) T cells, although reduced in numbers, were viable and could be analyzed further [9].
• Independent of their proliferation defect, Dicer-deficient helper T cells preferentially expressed interferon-gamma, the hallmark effector cytokine of the Th1 lineage [9].
• Dicer function is essential for lung epithelium morphogenesis [10].
• Using transgenes to drive Cre expression in discrete regions of the limb mesoderm, we find that removal of Dicer results in the loss of processed miRNAs [11].

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

• However, the mechanism by which DICER functions in the epithelium to influence Fgf10 expression in the mesenchyme remains unknown [10].

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