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miRNAs are required for generating a time delay critical for the circadian oscillator.

Title: miRNAs are required for generating a time delay critical for the circadian oscillator.
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Name(s): Chen, Rongmin, author
D'Alessandro, Matthew, author
Lee, Choogon, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2013-10-21
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Circadian clocks coordinate an organism's activities and regulate metabolic homeostasis in relation to daily environmental changes, most notably light/dark cycles. As in other organisms, the timekeeping mechanism in mammals depends on a self-sustaining transcriptional negative feedback loop with a built-in time delay in feedback inhibition. Although the time delay is essential for generating a slow, self-sustaining negative feedback loop with a period close to 24 hr, the exact mechanisms underlying the time delay are not known. Here, we show that RNAi mediated by microRNAs (miRNAs) is an essential mechanism in generating the time delay. In Dicer-deficient (and thus miRNA-deficient) cells and mice, circadian rhythms were dramatically shortened (by ∼2 hr), although the rhythms remained robust. The period shortening was caused by faster PER1 and PER2 translation in the Dicer-deficient cells. We also identified three specific miRNAs that regulate Per expression and showed that knockdown of these miRNAs in wild-type cells also shortened the circadian period. Consistent with the canonical function of miRNAs as translational modulators of target genes and their widespread roles in cell physiology, circadian rhythms are also modulated by miRNA-mediated RNAi acting on posttranscriptional regulation of key clock genes. Our present study definitively shows that RNAi is an important modulator of circadian rhythms by controlling the pace of PER synthesis and presents a novel layer of regulation for the clock.
Identifier: FSU_pmch_24094851 (IID), 10.1016/j.cub.2013.08.005 (DOI), PMC3809330 (PMCID), 24094851 (RID), 24094851 (EID), S0960-9822(13)00981-0 (PII)
Grant Number: DK-090730, R01 EY007739, R01 NS053616, NS-053616, R01 DK090730
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3809330.
Subject(s): Animals
Circadian Clocks
Gene Expression Regulation
Immunoblotting
Mice
Mice, Mutant Strains
MicroRNAs/genetics
MicroRNAs/metabolism
Period Circadian Proteins/genetics
Period Circadian Proteins/metabolism
Polymerase Chain Reaction
RNA Interference
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_24094851
Owner Institution: FSU
Is Part Of: Current biology : CB.
1879-0445
Issue: iss. 20, vol. 23

Choose the citation style.
Chen, R., D'Alessandro, M., & Lee, C. (2013). miRNAs are required for generating a time delay critical for the circadian oscillator. Current Biology : Cb. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_24094851