The miRNA machinery targets Mei-P26 and regulates Myc protein levels in the Drosophila wing

TY - JOUR

T1 - The miRNA machinery targets Mei-P26 and regulates Myc protein levels in the Drosophila wing

AU - Herranz, Héctor

AU - Hong, Xin

AU - Pérez, Lidia

AU - Ferreira, Ana

AU - Olivieri, Daniel

AU - Cohen, Stephen M

AU - Milán, Marco

PY - 2010/5/19

Y1 - 2010/5/19

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Cycle

KW - Cell Proliferation

KW - Drosophila Proteins

KW - Drosophila melanogaster

KW - E2F Transcription Factors

KW - Epithelium

KW - Female

KW - G1 Phase

KW - Genotype

KW - Male

KW - MicroRNAs

KW - Models, Biological

KW - Proto-Oncogene Proteins c-myc

KW - RNA Helicases

KW - Ribonuclease III

KW - S Phase

KW - Wing

U2 - 10.1038/emboj.2010.69

DO - 10.1038/emboj.2010.69

M3 - Journal article

C2 - 20400939

SN - 0261-4189

VL - 29

SP - 1688

EP - 1698

JO - E M B O Journal

JF - E M B O Journal

IS - 10

ER -