title: Achilles is a circadian clock-controlled gene that regulates immune function in Drosophila.
abstract: The circadian clock is a transcriptional/translational feedback loop that drives the rhythmic expression of downstream mRNAs. Termed "clock-controlled genes," these molecular outputs of the circadian clock orchestrate cellular, metabolic, and behavioral rhythms. As part of our on-going work to characterize key upstream regulators of circadian mRNA expression, we have identified a novel clock-controlled gene in Drosophila melanogaster, Achilles (Achl), which is rhythmic at the mRNA level in the brain and which represses expression of antimicrobial peptides in the immune system. Achilles knock-down in neurons dramatically elevates expression of crucial immune response genes, including IM1 (Immune induced molecule 1), Mtk (Metchnikowin), and Drs (Drosomysin). As a result, flies with knocked-down Achilles expression are resistant to bacterial challenges. Meanwhile, no significant change in core clock gene expression and locomotor activity is observed, suggesting that Achilles influences rhythmic mRNA outputs rather than directly regulating the core timekeeping mechanism. Notably, Achilles knock-down in the absence of immune challenge significantly diminishes the fly's overall lifespan, indicating a behavioral or metabolic cost of constitutively activating this pathway. Together, our data demonstrate that (1) Achilles is a novel clock-controlled gene that (2) regulates the immune system, and (3) participates in signaling from neurons to immunological tissues.
authors.affiliation: Department of Biology, University of Missouri - St. Louis, St. Louis, MO 63121, United States.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biology, University of Missouri - St. Louis, St. Louis, MO 63121, United States.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Terry
authors.affiliation: Department of Chemistry, University of Missouri - St. Louis, St. Louis, MO 63121, United States.
authors.forename: Edith
authors.initials: E
authors.lastname: Fejer
authors.affiliation: Department of Biology, University of Missouri - St. Louis, St. Louis, MO 63121, United States.
authors.forename: Diana
authors.initials: D
authors.lastname: Gamba
authors.affiliation: Department of Biology, University of Missouri - St. Louis, St. Louis, MO 63121, United States.
authors.forename: Natalie
authors.initials: N
authors.lastname: Hartmann
authors.affiliation: Department of Biology, University of Missouri - St. Louis, St. Louis, MO 63121, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Logsdon
authors.affiliation: Department of Biology, University of Missouri - St. Louis, St. Louis, MO 63121, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Michalski
authors.affiliation: Department of Biology, University of Missouri - St. Louis, St. Louis, MO 63121, United States.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Rois
authors.affiliation: Department of Chemistry, University of Missouri - St. Louis, St. Louis, MO 63121, United States.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Scuderi
authors.affiliation: Department of Genes - Circuits - Behavior, Max Planck Institute of Neurobiology, Martinsried, 82152, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kunst
authors.affiliation: Department of Biology, University of Missouri - St. Louis, St. Louis, MO 63121, United States. Electronic address: Michael.evan.hughes@gmail.com.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Hughes
mesh_terms: D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics*; D057906:Circadian Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000276:immunology; D007107:Immune System / Q000276:immunology*; D009474:Neurons / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D056926:CLOCK Proteins
keywords: Achilles; Antimicrobial peptides; Bacterial infection; CG17386; Circadian clock; Drosophila; Fat body; Gene expression; Genomics; Immunity; RNA-binding protein; RNA-seq