title: mir-11 limits the proapoptotic function of its host gene, dE2f1.
abstract: The E2F family of transcription factors regulates the expression of both genes associated with cell proliferation and genes that regulate cell death. The net outcome is dependent on cellular context and tissue environment. The mir-11 gene is located in the last intron of the Drosophila E2F1 homolog gene dE2f1, and its expression parallels that of dE2f1. Here, we investigated the role of miR-11 and found that miR-11 specifically modulated the proapoptotic function of its host gene, dE2f1. A mir-11 mutant was highly sensitive to dE2F1-dependent, DNA damage-induced apoptosis. Consistently, coexpression of miR-11 in transgenic animals suppressed dE2F1-induced apoptosis in multiple tissues, while exerting no effect on dE2F1-driven cell proliferation. Importantly, miR-11 repressed the expression of the proapoptotic genes reaper (rpr) and head involution defective (hid), which are directly regulated by dE2F1 upon DNA damage. In addition to rpr and hid, we identified a novel set of cell death genes that was also directly regulated by dE2F1 and miR-11. Thus, our data support a model in which the coexpression of miR-11 limits the proapoptotic function of its host gene, dE2f1, upon DNA damage by directly modulating a dE2F1-dependent apoptotic transcriptional program.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Truscott
authors.forename: Abul B M M K
authors.initials: AB
authors.lastname: Islam
authors.forename: Núria
authors.initials: N
authors.lastname: López-Bigas
authors.forename: Maxim V
authors.initials: MV
authors.lastname: Frolov
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation; D004249:DNA Damage / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009479:Neuropeptides / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C496298:E2f1 protein, Drosophila; C108880:HID protein, Drosophila; C561805:MIRN11 microRNA, Drosophila; D035683:MicroRNAs; D009479:Neuropeptides; D014157:Transcription Factors; C086973:rpr protein, Drosophila