title: ATAXIN-2 activates PERIOD translation to sustain circadian rhythms in Drosophila.
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.
authors.affiliation: Department of Neurobiology, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Chunghun
authors.initials: C
authors.lastname: Lim
authors.forename: Ravi
authors.initials: R
authors.lastname: Allada
mesh_terms: D000818:Animals; D000067528:Ataxins; D002460:Cell Line; D002940:Circadian Rhythm; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D056950:Period Circadian Proteins / Q000096:biosynthesis*; D039102:Poly(A)-Binding Proteins / Q000378:metabolism; D014176:Protein Biosynthesis; D034622:RNA Interference
chemical_list: D000067528:Ataxins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; C539040:PER protein, Drosophila; C526781:Pabp protein, Drosophila; D056950:Period Circadian Proteins; D039102:Poly(A)-Binding Proteins; C556188:tyf protein, Drosophila