JETLAG Resets the
            <i>Drosophila</i>
            Circadian Clock by Promoting Light-Induced Degradation of TIMELESS

Koh, Kyunghee; Zheng, X. Long; Sehgal, Amita

doi:10.1126/science.1124951

Cited by 259 publications

(338 citation statements)

References 24 publications

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“…An attractive possibility is that the higher mir-276a levels during the daytime are caused by light-mediated up-regulation of CF2 activity. This pathway might complement the more traditional pathways that also lower TIM levels in response to light (24,28,(32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

mir-276a strengthens Drosophila circadian rhythms by regulating timeless expression

Xiao

Rosbash

2016

Proc. Natl. Acad. Sci. U.S.A.

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Circadian rhythms in metazoan eukaryotes are controlled by an endogenous molecular clock. It functions in many locations, including subsets of brain neurons (clock neurons) within the central nervous system. Although the molecular clock relies on transcription/translation feedback loops, posttranscriptional regulation also plays an important role. Here, we show that the abundant Drosophila melanogaster microRNA mir-276a regulates molecular and behavioral rhythms by inhibiting expression of the important clock gene timeless (tim). Misregulation of mir-276a in clock neurons alters tim expression and increases arrhythmicity under standard constant darkness (DD) conditions. mir-276a expression itself appears to be light-regulated because its levels oscillate under 24-h light-dark (LD) cycles but not in DD. mir-276a is regulated by the transcription activator Chorion factor 2 in flies and in tissue-culture cells. Evidence from flies mutated using the clustered, regularly interspaced, short palindromic repeats (CRISPR) tool shows that mir-276a inhibits tim expression: Deleting the mir276a-binding site in the tim 3′ UTR causes elevated levels of TIM and ∼50% arrhythmicity. We suggest that this pathway contributes to the more robust rhythms observed under light/dark LD conditions than under DD conditions. microRNA | circadian rhythms | light regulation | CRISPR

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Section: Discussionmentioning

confidence: 99%

mir-276a strengthens Drosophila circadian rhythms by regulating timeless expression

Xiao

Rosbash

2016

Proc. Natl. Acad. Sci. U.S.A.

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“…2) (Naidoo et al 1999;Lin et al 2001), but until recently, other molecular components of this response were not known. We recently identified one such component through the analysis of a mutation found in one of our fly stocks (Koh et al 2006a). This particular stock showed reduced sensitivity to light such that it was rhythmic in the presence of constant light (wild-type flies are arrhythmic under these conditions) (Fig.…”

Section: Entrainment Of the Clock To Lightmentioning

confidence: 99%

Molecular Analysis of Sleep: Wake Cycles inDrosophila

Sehgal¹,

Joiner²,

Crocker³

et al. 2007

Cold Spring Harbor Symposia on Quantitative Biology

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“…Light exposure causes a conformational change in CRY that allows it to bind TIM. TIM is phosphorylated on at least one tyrosine residue and interacts with the JETLAG (JET) protein, which targets TIM for ubiquitination and degradation by the proteasome pathway (Koh et al 2006). …”

Section: Drosophila Melanogastermentioning

confidence: 99%

Biological Rhythms Workshop IA: Molecular Basis of Rhythms Generation

Mackey¹

2007

Cold Spring Harbor Symposia on Quantitative Biology

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Current circadian models are based on genetic, biochemical, and structural data that, when combined, provide a comprehensive picture of the molecular basis for rhythms generation. These models describe three basic elements-input pathways, oscillator, and output pathways-to which each molecular component is assigned. The lines between these elements are often blurred because some proteins function in more than one element of the circadian system. The end result of these molecular oscillations is the same in each system (near 24-hour timing), yet the proteins involved, the interactions among those proteins, and the regulatory feedback loops differ. Here, the current models for the molecular basis for rhythms generation are described for the prokaryotic cyanobacterium Synechococcus elongatus as well as the eukaryotic systems Neurospora crassa, Drosophila melanogaster, Arabidopsis thaliana, and mammals (particularly rodents).

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JETLAG Resets the Drosophila Circadian Clock by Promoting Light-Induced Degradation of TIMELESS

Cited by 259 publications

References 24 publications

mir-276a strengthens Drosophila circadian rhythms by regulating timeless expression

mir-276a strengthens Drosophila circadian rhythms by regulating timeless expression

Molecular Analysis of Sleep: Wake Cycles inDrosophila

Biological Rhythms Workshop IA: Molecular Basis of Rhythms Generation

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