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Lim, Chunghun
Neurogenetics & Ribonomics Laboratory (The Lim Lab)
Research Interests
  • Post-transcriptional Gene Expression, Neurodegeneration, Behavioral Genetics

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

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Title
ATAXIN-2 activates PERIOD translation to sustain circadian rhythms in Drosophila
Author
Lim, ChunghunAllada, Ravi
Keywords
GENE; CLOCK; NEURONS; REPEAT; TYPE-2; EXPANSION; PATHOLOGY; HOMOLOG; PROTEIN; CLONING
Issue Date
201305
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Citation
SCIENCE, v.340, no.6134, pp.875 - 879
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.
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DOI
http://dx.doi.org/10.1126/science.1234785
ISSN
0036-8075
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