The Oscillating miRNA 959-964 Cluster Impacts Drosophila Feeding Time and Other Circadian Outputs

Vodala, Sadanand; Pescatore, Stefan; Rodriguez, Joseph; Buescher, Marita; Chen, Yawen; Weng, Ruifen; Cohen, Stephen M.; Rosbash, Michael

doi:10.1016/j.cmet.2012.10.002

Cited by 58 publications

(76 citation statements)

References 55 publications

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“…However, only a few have been reported to affect fly circadian rhythms (16)(17)(18)(19)(20)26). Although most of these control clock output pathways, two abundant miRNAs, bantam and let-7, directly target core clock proteins, CLK and CLOCKWORK ORANGE (CWO), respectively (16,20).…”

Section: Discussionmentioning

confidence: 99%

“…A relatively short half-life is a prerequisite for circadian cycling of an RNA, because miRNAs generally are quite stable, and this requirement explains why only a few of them have been reported as being rhythmically expressed (16)(17)(18). [Mammalian neurons may be exceptional in having many miRNAs with short half-lives (31).]…”

Section: Discussionmentioning

confidence: 99%

“…mir-276a was basically quantified as described in ref. 17, except that MasterCycler RealPlex was used for quantification.…”

Section: Methodsmentioning

confidence: 99%

“…miRNAs generally base pair with the 3′ UTR of mRNAs; this interaction triggers mRNA degradation and/or translational inhibition, leading to decreased levels of gene expression (15). To date, only a few examples of miRNAs regulating circadian gene expression in Drosophila have been reported (16)(17)(18)(19)(20).…”

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confidence: 99%

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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%

Section: Discussionmentioning

confidence: 99%

“…mir-276a was basically quantified as described in ref. 17, except that MasterCycler RealPlex was used for quantification.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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

Xiao

Rosbash

2016

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

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“…In addition, knockdown of the miRNA effector GW182 caused circadian defects via defective PDF signaling . Individual fly miRNA knock-outs, including let-7 (Chen et al, 2014), mir-959ϳ964 (Vodala et al, 2012), andmir-279/mir-996 (Luo andSehgal, 2012;Sun et al, 2015b), affect various aspects of rhythmic behavior.…”

Section: Introductionmentioning

confidence: 99%

miR-124 Regulates Diverse Aspects of Rhythmic Behavior inDrosophila

Garaulet

Sun

et al. 2016

J. Neurosci.

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Circadian clocks enable organisms to anticipate and adapt to fluctuating environmental conditions. Despite substantial knowledge of central clock machineries, we have less understanding of how the central clock's behavioral outputs are regulated. Here, we identify Drosophila miR-124 as a critical regulator of diurnal activity. During normal light/dark cycles, mir-124 mutants exhibit profoundly abnormal locomotor activity profiles, including loss of anticipatory capacities at morning and evening transitions. Moreover, mir-124 mutants exhibited striking behavioral alterations in constant darkness (DD), including a temporal advance in peak activity. Nevertheless, anatomical and functional tests demonstrate a normal circadian pacemaker in mir-124 mutants, indicating this miRNA regulates clock output. Among the extensive miR-124 target network, heterozygosity for targets in the BMP pathway substantially corrected the evening activity phase shift in DD. Thus, excess BMP signaling drives specific circadian behavioral output defects in mir-124 knock-outs.

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