The miRNA machinery targets Mei-P26 and regulates Myc protein levels in the Drosophila wing.
MicroRNAs (miRNAs) have been implicated in cell-cycle regulation and in some cases shown to have a role in tissue growth control. Depletion of miRNAs was found to have an effect on tissue growth rates in the wing primordium of Drosophila, a highly proliferative epithelium. Dicer-1 (Dcr-1) is a double-stranded RNAseIII essential for miRNA biogenesis. Adult cells lacking dcr-1, or with reduced dcr-1 activity, were smaller than normal cells and gave rise to smaller wings. dcr-1 mutant cells showed evidence of being susceptible to competition by faster growing cells in vivo and the miRNA machinery was shown to promote G(1)-S transition. We present evidence that Dcr-1 acts by regulating the TRIM-NHL protein Mei-P26, which in turn regulates dMyc protein levels. Mei-P26 is a direct target of miRNAs, including the growth-promoting bantam miRNA. Thus, regulation of tissue growth by the miRNA pathway involves a double repression mechanism to control dMyc protein levels in a highly proliferative and growing epithelium.
Herranz
Héctor
H
Cell and Developmental Biology Programme, Institute for Research in Biomedicine, Barcelona, Spain.
Hong
Xin
X
Pérez
Lidia
L
Ferreira
Ana
A
Olivieri
Daniel
D
Cohen
Stephen M
SM
Milán
Marco
M
D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D050684:E2F Transcription Factors / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005260:Female; D016193:G1 Phase; D005838:Genotype; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008954:Models, Biological; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D020365:RNA Helicases / Q000378:metabolism*; D043244:Ribonuclease III / Q000378:metabolism*; D016196:S Phase; D014921:Wings, Animal / Q000378:metabolism
D029721:Drosophila Proteins; D050684:E2F Transcription Factors; C530643:Mei-P26 protein, Drosophila; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; C515033:Dcr-1 protein, Drosophila; D043244:Ribonuclease III; D020365:RNA Helicases
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