Conserved MicroRNA miR-8/miR-200 and Its Target USH/FOG2 Control Growth by Regulating PI3K

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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 p85 alpha, 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.
Publisher
Cell Press
Issue Date
2009-12
Language
English
Article Type
Article
Keywords

ZINC-FINGER PROTEINS; DROSOPHILA-MELANOGASTER; TRANSCRIPTION FACTORS; PROTHORACIC GLAND; INSULIN; FOG-2; CANCER; FRIEND; SIZE; EXPRESSION

Citation

CELL, v.139, no.6, pp.1096 - 1108

ISSN
0092-8674
DOI
10.1016/j.cell.2009.11.020
URI
http://hdl.handle.net/10203/96729
Appears in Collection
BS-Journal Papers(저널논문)
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