Modulation of ionizing radiation-induced apoptosis by bantam microRNA in Drosophila

Abstract

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.

mir-11 limits the proapoptotic function of its host gene, dE2f1

“…Our data suggest that such regulation could be also mediated by microRNAs, and in Drosophila, mir-11 would play this role. Although there are other microRNAs that inhibit apoptosis (Brennecke et al 2003;Xu et al 2003;Leaman et al 2005;Jaklevic et al 2008), the coexpression of mir-11 with dE2f1 puts miR-11 in a special position, since it would be expressed precisely where and when dE2F1 is expressed. To our knowledge, this is the first example of an imbedded intronic microRNA regulating direct gene targets of its transcription factor host.…”

Identification of highly expressed host microRNAs that respond to white spot syndrome virus infection in the Pacific white shrimp Litopenaeus vannamei (Penaeidae)

“…These host miRNAs are involved in virus-host interactions, most of which are related to host immune responses. Among the differentially expressed miRNAs, the most highly expressed miRNA is dme-bantam-3p, which belongs to the bantam family, a family of miRNAs that has been shown to affect tissue growth by stimulating cell proliferation and inhibiting cell apoptosis in Drosophila (Thompson and Cohen, 2006;Jaklevic et al, 2008). In the present study, dme-bantam-3p was expressed 0.30-fold greater in the infected library than in the uninfected library, indicating that WSSV may stimulate apoptosis of host cells by inhibiting the expression of bantam family members.…”

The Sound of Silence

“…Jaklevic et al (2008) first noted that ionizing radiation of the developing wing disc generally increases the levels of bantam , a microRNA that stimulates cell proliferation and inhibits apoptosis by repressing the proapoptotic factor hid (Brennecke, Hipfner, Stark, Russell, & Cohen, 2003; Jaklevic et al, 2008). Additionally, bantam null animals were exceptionally susceptible to ionizing radiation, exhibiting increased apoptosis.…”