Micro-Managing the Circadian Clock: The Role of microRNAs in Biological Timekeeping

Mehta, Neel; Cheng, Hai-Ying Mary

doi:10.1016/j.jmb.2012.10.022

Cited by 78 publications

(68 citation statements)

References 92 publications

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“…Period proteins are thought to predominantly control circadian rhythms by acting on protein-coding gene targets, though circadian clocks have been shown to impact miRNA biogenesis pathways at multiple steps and miRNAs have been found to post-transcriptionally regulate core circadian clock feedback loops. [22][23][24] Studies have also found that miRNAs can be influenced by core circadian oscillator components in Drosophila and mammals. 24 For example, miR-279 has recently been shown to impact JAK/ STAT signaling and thus rest/activity circadian rhythms in Drosophila, 25 and miR-219-1 was found to be a direct transcriptional target of the oscillator protein CLOCK.…”

Section: Discussionmentioning

confidence: 99%

“…[22][23][24] Studies have also found that miRNAs can be influenced by core circadian oscillator components in Drosophila and mammals. 24 For example, miR-279 has recently been shown to impact JAK/ STAT signaling and thus rest/activity circadian rhythms in Drosophila, 25 and miR-219-1 was found to be a direct transcriptional target of the oscillator protein CLOCK. 24 The new findings by Van Wynsberghe et al and Perales et al nicely show that the effects of the circadian oscillator on miRNA expression encompass more than just a few miRNAs, but instead transcriptionally regulate a large group of miRNAs and other mRNAs to ultimately 15,16 Additionally, little is known about how LIN-42 is regulated to cause its oscillatory expression pattern throughout development.…”

Section: Discussionmentioning

confidence: 99%

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Period homolog LIN-42 regulates miRNA transcription to impact developmental timing

Wynsberghe¹,

Pasquinelli²

2014

Worm

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Expression from both a let-7 miRNA and a lin-4 miRNA transcriptional reporter were enhanced in the absence of lin-42. Additionally, chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) of late larval stage worms showed that LIN-42 bound the let-7 promoter, suggesting that LIN-42 affects mature miRNA levels by inhibiting their transcription. In addition to miRNAs, LIN-42 also predominantly bound to the promoters of many diverse protein-coding genes. These findings support the action of LIN-42 at multiple points within the heterochronic and other regulatory pathways to impact a multitude of functions including developmental timing.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Period homolog LIN-42 regulates miRNA transcription to impact developmental timing

Wynsberghe¹,

Pasquinelli²

2014

Worm

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“…For example, 193 of the 263 fly head mRNAs with cycling expression had lower amplitudes or even flat expression at the nascent RNA levels (9). MicroRNA (miRNA) regulation is an important type of posttranscriptional regulation (14) that might influence the oscillations of mRNAs and/or proteins. 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).…”

mentioning

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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“…Beyond the abundant information on the transcriptionaltranslation feedback loops of circadian rhythms, the importance of post-transcriptional mechanisms is increasingly recognized in circadian rhythms 20,21 , such as regulation by microRNAs (miRNAs) 22 . The miRNAs are endogenous small non-coding RNAs (19-25 nt) that function in post-transcriptional regulation of gene expression, and are found to target more than 30% of all protein-coding mRNAs in mammals 23,24 .…”

mentioning

confidence: 99%

Regulation of Drosophila circadian rhythms by miRNA let-7 is mediated by a regulatory cycle

et al. 2014

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MicroRNA-mediated post-transcriptional regulations are increasingly recognized as important components of the circadian rhythm. Here we identify microRNA let-7, part of the Drosophila let-7-Complex, as a regulator of circadian rhythms mediated by a circadian regulatory cycle. Overexpression of let-7 in clock neurons lengthens circadian period and its deletion attenuates the morning activity peak as well as molecular oscillation. Let-7 regulates the circadian rhythm via repression of CLOCKWORK ORANGE (CWO). Conversely, upregulated cwo in cwo-expressing cells can rescue the phenotype of let-7-Complex overexpression. Moreover, circadian prothoracicotropic hormone (PTTH) and CLOCKregulated 20-OH ecdysteroid signalling contribute to the circadian expression of let-7 through the 20-OH ecdysteroid receptor. Thus, we find a regulatory cycle involving PTTH, a direct target of CLOCK, and PTTH-driven miRNA let-7.

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Micro-Managing the Circadian Clock: The Role of microRNAs in Biological Timekeeping

Cited by 78 publications

References 92 publications

Period homolog LIN-42 regulates miRNA transcription to impact developmental timing

Period homolog LIN-42 regulates miRNA transcription to impact developmental timing

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

Regulation of Drosophila circadian rhythms by miRNA let-7 is mediated by a regulatory cycle

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