title: A novel pathway for sensory-mediated arousal involves splicing of an intron in the period clock gene.
abstract: OBJECTIVE
  D. melanogaster is an excellent animal model to study how the circadian (≅24-h) timing system and sleep regulate daily wake-sleep cycles. Splicing of a temperature-sensitive 3'-terminal intron (termed dmpi8) from the circadian clock gene period (per) regulates the distribution of daily activity in Drosophila. The role of dmpi8 splicing on daily behavior was further evaluated by analyzing sleep.
  
  
  METHODS
  Transgenic flies of the same genetic background but expressing either a wild-type recombinant per gene or one where the efficiency of dmpi8 splicing was increased were exposed to different temperatures in daily light-dark cycles and sleep parameters measured. In addition, transgenic flies were briefly exposed to a variety of sensory-mediated stimuli to measure arousal responses.
  
  
  RESULTS
  Surprisingly, we show that the effect of dmpi8 splicing on daytime activity levels does not involve a circadian role for per but is linked to adjustments in sensory-dependent arousal and sleep behavior. Genetically altered flies with high dmpi8 splicing efficiency remain aroused longer following short treatments with light and non-photic cues such as mechanical stimulation.
  
  
  CONCLUSIONS
  We propose that the thermal regulation of dmpi8 splicing acts as a temperature-calibrated rheostat in a novel arousal mechanism, so that on warm days the inefficient splicing of the dmpi8 intron triggers an increase in quiescence by decreasing sensory-mediated arousal, thus ensuring flies minimize being active during the hot midday sun despite the presence of light in the environment, which is usually a strong arousal cue for diurnal animals.
authors.affiliation: Rutgers University, Center for Advanced Biotechnology and Medicine, Piscataway, NJ.
authors.forename: Weihuan
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Molecular Biology and Biochemistry, Rutgers University, Center for Advanced Biotechnology and Medicine, Piscataway, NJ.
authors.forename: Isaac
authors.initials: I
authors.lastname: Edery
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001143:Arousal / Q000235:genetics* / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D003463:Cues; D003624:Darkness; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000502:physiology*; D005260:Female; D007438:Introns / Q000235:genetics*; D008027:Light; D008297:Male; D056950:Period Circadian Proteins / Q000235:genetics* / Q000378:metabolism; D010812:Physical Stimulation; D012326:RNA Splicing / Q000235:genetics*; D012890:Sleep / Q000235:genetics / Q000502:physiology; D013696:Temperature; D014851:Wakefulness / Q000235:genetics / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins
keywords: Drosophila; arousal; circadian rhythms; light; period gene; pre-mRNA splicing; sleep; temperature