Modulation of ionizing radiation-induced apoptosis by bantam microRNA in Drosophila.
In Drosophila, heterozygosity in the pro-apoptotic gene hid significantly reduces apoptosis that is induced by ionizing radiation (IR). Therefore, mechanisms that regulate Hid levels can potentially contribute to life-or-death decision of an irradiated cell. 3'UTR of hid mRNA contains 5 potential binding sites for bantam microRNA. Ectopic expression of ban attenuated apoptosis that results from ectopic expression of hid but the significance of this regulation under physiological conditions remained to be investigated. We report here that ban is needed to limit IR-induced apoptosis in larval imaginal discs. Using tubulin-EGFP ban sensors with ban consensus sequences in the 3'UTR, we find that EGFP decreases following IR, indicating that IR activates ban. Likewise, a tubulin-EGFP reporter with hid-3'UTR is repressed in irradiated discs and this repression requires ban consensus sites in the hid 3'UTR. ban mutant larvae show increased sensitivity to killing by IR, which is suppressed by a mutation in hid. These results can fit into a model in which IR activates ban and ban represses hid to limit IR-induced apoptosis. miRNAs have been shown previously to be induced by radiation but this is the first report that a miRNA is functionally important for radiation responses.
Jaklevic
Burnley
B
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309-0347, USA.
Uyetake
Lyle
L
Wichmann
Anita
A
Bilak
Amber
A
English
Christopher N
CN
Su
Tin Tin
TT
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000528:radiation effects*; D018628:Gene Dosage / Q000528:radiation effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009479:Neuropeptides / Q000378:metabolism; D011839:Radiation, Ionizing; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014921:Wings, Animal / Q000166:cytology / Q000528:radiation effects
D020413:3' Untranslated Regions; D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D035683:MicroRNAs; D009479:Neuropeptides; D016159:Tumor Suppressor Protein p53; C471146:bantam microRNA, Drosophila; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins