Conserved MicroRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K.
How body size is determined is a long-standing question in biology, yet its regulatory mechanisms remain largely unknown. Here, we find that a conserved microRNA miR-8 and its target, USH, regulate body size in Drosophila. miR-8 null flies are smaller in size and defective in insulin signaling in fat body that is the fly counterpart of liver and adipose tissue. Fat body-specific expression and clonal analyses reveal that miR-8 activates PI3K, thereby promoting fat cell growth cell-autonomously and enhancing organismal growth non-cell-autonomously. Comparative analyses identify USH and its human homolog, FOG2, as the targets of fly miR-8 and human miR-200, respectively. USH/FOG2 inhibits PI3K activity, suppressing cell growth in both flies and humans. FOG2 directly binds to p85alpha, the regulatory subunit of PI3K, and interferes with the formation of a PI3K complex. Our study identifies two novel regulators of insulin signaling, miR-8/miR-200 and USH/FOG2, and suggests their roles in adolescent growth, aging, and cancer.
Hyun
Seogang
S
School of Biological Sciences and National Creative Research Center, Seoul National University, Seoul, 151-742, Korea.
Lee
Jung Hyun
JH
Jin
Hua
H
Nam
JinWu
J
Namkoong
Bumjin
B
Lee
Gina
G
Chung
Jongkyeong
J
Kim
V Narry
VN
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D049628:Body Size; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D035683:MicroRNAs; D014157:Transcription Factors; C117427:ZFPM2 protein, human; C526630:MIRN8 microRNA, Drosophila; C109258:ush protein, Drosophila; D019869:Phosphatidylinositol 3-Kinases