A novel pathway for sensory-mediated arousal involves splicing of an intron in the period clock gene.

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. 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. 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. 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.

Cao W ，Edery I 《-》

Natural variation in the Drosophila melanogaster clock gene period modulates splicing of its 3'-terminal intron and mid-day siesta.

Low KH ，Chen WF ，Yildirim E ，Edery I ... -  《PLoS One》

Mid-day siesta in natural populations of D. melanogaster from Africa exhibits an altitudinal cline and is regulated by splicing of a thermosensitive intron in the period clock gene.

Cao W ，Edery I 《BMC EVOLUTIONARY BIOLOGY》

The SR protein B52/SRp55 regulates splicing of the period thermosensitive intron and mid-day siesta in Drosophila.

Zhang Z ，Cao W ，Edery I 《Scientific Reports》

Daywake, an Anti-siesta Gene Linked to a Splicing-Based Thermostat from an Adjoining Clock Gene.

Sleep is fundamental to animal survival but is a vulnerable state that also limits how much time can be devoted to critical wake-dependent activities [1]. Although many animals are day-active and sleep at night, they exhibit a midday nap, or "siesta," that can vary in intensity and is usually more prominent on warm days. In humans, the balance between maintaining the wake state or sleeping during the day has important health implications [2], but the mechanisms underlying this dynamic regulation are poorly understood. Using the well-established Drosophila melanogaster animal model to study sleep [3], we identify a new wake-sleep regulator that we term daywake (dyw). dyw encodes a juvenile hormone-binding protein [4] that functions in neurons as a day-specific anti-siesta gene, with little effect on sleep levels during the nighttime or in the absence of light. Remarkably, dyw expression is stimulated in trans via cold-enhanced splicing of the dmpi8 intron [5] from the reverse-oriented but slightly overlapping period (per) clock gene [6]. The functionally integrated dmpi8-dyw genetic unit operates as a "behavioral temperate acclimator" by increasingly counterbalancing siesta-promoting pathways as daily temperatures become cooler and carry reduced risks from daytime heat exposure. While daily patterns of when animals are awake and when they sleep are largely scheduled by the circadian timing system, dyw implicates a less recognized class of modulatory wake-sleep regulators that primarily function to enhance flexibility in wake-sleep preference, a behavioral plasticity that is commonly observed in animals during the midday, raising the possibility of shared mechanisms.

Yang Y ，Edery I 《-》