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A Role for Drosophila ATX2 in Activation of PER Translation and Circadian Behavior

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Science  17 May 2013:
Vol. 340, Issue 6134, pp. 879-882
DOI: 10.1126/science.1234746

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ATAXIN Clock

Although core components of circadian clocks in flies and mammals are transcriptional circuits, recent evidence indicates posttranscriptional regulation of the clock occurs. Studies from Lim and Allada (p. 875) and Zhang et al. (p. 879) converge to show that the protein ATAXIN-2, associated with neurodegenerative diseases in humans, is a regulator of translation required for normal clock function in pacemaker neurons and for daily rhythms of behavior. ATAXIN is an RNA-binding protein and cooperates in the accumulation of the Per (Period) protein, a core transcriptional regulatory component of the clock.

Abstract

A negative transcriptional feedback loop generates circadian rhythms in Drosophila. PERIOD (PER) is a critical state-variable in this mechanism, and its abundance is tightly regulated. We found that the Drosophila homolog of ATAXIN-2 (ATX2)—an RNA-binding protein implicated in human neurodegenerative diseases—was required for circadian locomotor behavior. ATX2 was necessary for PER accumulation in circadian pacemaker neurons and thus determined period length of circadian behavior. ATX2 was required for the function of TWENTY-FOUR (TYF), a crucial activator of PER translation. ATX2 formed a complex with TYF and promoted its interaction with polyadenylate-binding protein (PABP). Our work uncovers a role for ATX2 in circadian timing and reveals that this protein functions as an activator of PER translation in circadian neurons.

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