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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 301 - 312 (12page)
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초록· 키워드
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Post-transcriptional regulation underlies the circadian control of gene expression and animal behaviors. However, the role of mRNA surveillance via the nonsense-mediated mRNA decay (NMD) pathway in circadian rhythms remains elusive. Here, we report that Drosophila NMD pathway acts in a subset of circadian pacemaker neurons to maintain robust 24h rhythms of free-running locomotor activity. RNA interference-mediated depletion of key NMD factors in timeless-expressing clock cells decreased the amplitude of circadian locomotor behaviors. Transgenic manipulation of the NMD pathway in clock neurons expressing a neuropeptide PIGMENT-DISPERSING FACTOR (PDF) was sufficient to dampen or lengthen free-running locomotor rhythms. Confocal imaging of a transgenic NMD reporter revealed that arrhythmic Clock mutants exhibited stronger NMD activity in PDF-expressing neurons than wild-type. We further found that hypomorphic mutations in Suppressor with morphogenetic effect on genitalia 5 (Smg5) or Smg6 impaired circadian behaviors. These NMD mutants normally developed PDF-expressing clock neurons and displayed daily oscillations in the transcript levels of core clock genes. By contrast, the loss of Smg5 or Smg6 function affected the relative transcript levels of cAMP response element-binding protein B (CrebB) in an isoform-specific manner. Moreover, the overexpression of a transcriptional repressor form of CrebB rescued free-running locomotor rhythms in Smg5-depleted flies. These data demonstrate that CrebB is a rate-limiting substrate of the genetic NMD pathway important for the behavioral output of circadian clocks in Drosophila.
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참고문헌 (98)
참고문헌 신청
Agostino, P. V. / 2011 / Unwinding the molecular basis of interval and circadian timing / Front. Integr. Neurosci 5:64
Allada, R. / 1998 / A mutant Drosophila homolog of mammalian clock disrupts circadian rhythms and transcription of period and timeless / Cell 93:791~804
Alonso, C. R. / 2005 / Nonsense-mediated RNA decay : a molecular system micromanaging individual gene activities and suppressing genomic noise / Bioessays 27:463~466
Aronson, B. D. / 1994 / Negative feedback defining a circadian clock : autoregulation of the clock gene frequency / Science 263:1578~1584
Avery, P. / 2011 / Drosophila Upf1 and Upf2 loss of function inhibits cell growth and causes animal death in a Upf3-independent manner / RNA 17:624~638
Allada, R. / 1998 / A mutant Drosophila homolog of mammalian clock disrupts circadian rhythms and transcription of period and timeless / Cell 93:791~804
Alonso, C. R. / 2005 / Nonsense-mediated RNA decay : a molecular system micromanaging individual gene activities and suppressing genomic noise / Bioessays 27:463~466
Aronson, B. D. / 1994 / Negative feedback defining a circadian clock : autoregulation of the clock gene frequency / Science 263:1578~1584
Avery, P. / 2011 / Drosophila Upf1 and Upf2 loss of function inhibits cell growth and causes animal death in a Upf3-independent manner / RNA 17:624~638
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