TY - JOUR
T1 - NEMO kinase contributes to core period determination by slowing the pace of the drosophila circadian oscillator
AU - Yu, Wangjie
AU - Houl, Jerry H.
AU - Hardin, Paul E.
N1 - Funding Information:
We thank the Vienna Drosophila RNAi Center for providing the nmo RNAi flies, E. Verheyen for providing UAS-GFP- nmo flies, I. Edery for sharing unpublished results, and the Bloomington Drosophila Stock Center for providing the P{lacW} nmo P1 , Df(3L)Exel6279, P{UAS-Dcr-2.D}, and tub Gal80 ts flies. This work was supported by National Institutes of Health grant NS052854.
PY - 2011/5/10
Y1 - 2011/5/10
N2 - The Drosophila circadian oscillator is comprised of transcriptional feedback loops that are activated by CLOCK (CLK) and CYCLE (CYC) and repressed by PERIOD (PER) and TIMELESS (TIM) [1]. The timing of CLK-CYC activation and PER-TIM repression is regulated posttranslationally, in part through rhythmic phosphorylation of CLK, PER, and TIM [2-4]. Although kinases that control PER and TIM levels and subcellular localization have been identified [5-10], additional kinases are predicted to target PER, TIM, and/or CLK to promote time-specific transcriptional repression. We screened for kinases that alter circadian behavior via clock cell-directed RNA interference (RNAi) and identified the proline-directed kinase nemo (nmo) as a novel component of the circadian oscillator. Both nmo RNAi knockdown and a nmo hypomorphic mutant shorten circadian period, whereas nmo overexpression lengthens circadian period. CLK levels increase when nmo expression is knocked down in clock cells, whereas CLK levels decrease and PER and TIM accumulation are delayed when nmo is overexpressed in clock cells. These data suggest that nmo slows the pace of the circadian oscillator by altering CLK, PER, and TIM expression, thereby contributing to the generation of an ∼24 hr circadian period.
AB - The Drosophila circadian oscillator is comprised of transcriptional feedback loops that are activated by CLOCK (CLK) and CYCLE (CYC) and repressed by PERIOD (PER) and TIMELESS (TIM) [1]. The timing of CLK-CYC activation and PER-TIM repression is regulated posttranslationally, in part through rhythmic phosphorylation of CLK, PER, and TIM [2-4]. Although kinases that control PER and TIM levels and subcellular localization have been identified [5-10], additional kinases are predicted to target PER, TIM, and/or CLK to promote time-specific transcriptional repression. We screened for kinases that alter circadian behavior via clock cell-directed RNA interference (RNAi) and identified the proline-directed kinase nemo (nmo) as a novel component of the circadian oscillator. Both nmo RNAi knockdown and a nmo hypomorphic mutant shorten circadian period, whereas nmo overexpression lengthens circadian period. CLK levels increase when nmo expression is knocked down in clock cells, whereas CLK levels decrease and PER and TIM accumulation are delayed when nmo is overexpressed in clock cells. These data suggest that nmo slows the pace of the circadian oscillator by altering CLK, PER, and TIM expression, thereby contributing to the generation of an ∼24 hr circadian period.
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U2 - 10.1016/j.cub.2011.02.037
DO - 10.1016/j.cub.2011.02.037
M3 - Article
C2 - 21514156
AN - SCOPUS:79955544537
SN - 0960-9822
VL - 21
SP - 756
EP - 761
JO - Current Biology
JF - Current Biology
IS - 9
ER -