Achilles is a circadian clock-controlled gene that regulates immune function in Drosophila

Jiajia Li, Erin E. Terry, Edith Fejer, Diana Gamba, Natalie Hartmann, Joseph Logsdon, Daniel Michalski, Lisa E. Rois, Maria J. Scuderi, Michael Kunst, Michael E. Hughes

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish
Pages (from-to)127-136
Number of pages10
JournalBrain, Behavior, and Immunity
Volume61
DOIs
StatePublished - Mar 1 2017

Keywords

  • Achilles
  • Antimicrobial peptides
  • Bacterial infection
  • CG17386
  • Circadian clock
  • Drosophila
  • Fat body
  • Gene expression
  • Genomics
  • Immunity
  • RNA-binding protein
  • RNA-seq

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