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: Chunghun Lim, Ravi Allada
• Journal: Science (New York, N.Y.) (Science) Vol. 340 Issue 6134 Pg. 875-9 (May 17 2013) ISSN: 1095-9203 [Electronic] United States
• PMID: 23687047 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

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

Topics

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