ATAXIN-2 activates PERIOD translation to sustain circadian rhythms in Drosophila

Science. 2013 May 17;340(6134):875-9. doi: 10.1126/science.1234785.

Abstract

Evidence for transcriptional feedback in circadian timekeeping is abundant, yet little is known about the mechanisms underlying translational control. We found that ATAXIN-2 (ATX2), an RNA-associated protein involved in neurodegenerative disease, is a translational activator of the rate-limiting clock component PERIOD (PER) in Drosophila. ATX2 specifically interacted with TWENTY-FOUR (TYF), an activator of PER translation. RNA interference-mediated depletion of Atx2 or the expression of a mutant ATX2 protein that does not associate with polyadenylate-binding protein (PABP) suppressed behavioral rhythms and decreased abundance of PER. Although ATX2 can repress translation, depletion of Atx2 from Drosophila S2 cells inhibited translational activation by RNA-tethered TYF and disrupted the association between TYF and PABP. Thus, ATX2 coordinates an active translation complex important for PER expression and circadian rhythms.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Ataxins
  • Cell Line
  • Circadian Rhythm*
  • Drosophila Proteins / biosynthesis*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / metabolism
  • Drosophila melanogaster / physiology*
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Period Circadian Proteins / biosynthesis*
  • Poly(A)-Binding Proteins / metabolism
  • Protein Biosynthesis
  • RNA Interference

Substances

  • Ataxins
  • Drosophila Proteins
  • Nerve Tissue Proteins
  • PER protein, Drosophila
  • Pabp protein, Drosophila
  • Period Circadian Proteins
  • Poly(A)-Binding Proteins
  • tyf protein, Drosophila