Role of miR-142-3p in the post-transcriptional regulation of the clock gene Bmal1 in the mouse SCN.

MicroRNAs (miRNAs) are small non-coding RNAs that function as post-transcriptional modulators by regulating stability or translation of target mRNAs. Recent studies have implicated miRNAs in the regulation of mammalian circadian rhythms. To explore the role of miRNAs in the post-transcriptional modu...

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Main Authors: Vikram R Shende, Nichole Neuendorff, David J Earnest
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3673942?pdf=render
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author Vikram R Shende
Nichole Neuendorff
David J Earnest
author_facet Vikram R Shende
Nichole Neuendorff
David J Earnest
author_sort Vikram R Shende
collection DOAJ
description MicroRNAs (miRNAs) are small non-coding RNAs that function as post-transcriptional modulators by regulating stability or translation of target mRNAs. Recent studies have implicated miRNAs in the regulation of mammalian circadian rhythms. To explore the role of miRNAs in the post-transcriptional modulation of core clock genes in the master circadian pacemaker, we examined miR-142-3p for evidence of circadian expression in the suprachiasmatic nuclei (SCN), regulation of its putative clock gene target Bmal1 via specific binding sites in the 3' UTR and overexpression-induced changes in the circadian rhythm of BMAL1 protein levels in SCN cells. In mice exposed to constant darkness (DD), miR-142-3p levels in the SCN were characterized by circadian rhythmicity with peak expression during early subjective day at CT 3. Mutagenesis studies indicate that two independent miRNA recognition elements located at nucleotides 1-7 and 335-357 contribute equally to miR-142-3p-induced repression of luciferase-reported Bmal1 3' UTR activity. Importantly, overexpression of miR-142-3p in immortalized SCN cells abolished circadian variation in endogenous BMAL1 protein levels in vitro. Collectively, our results suggest that miR-142-3p may play a role in the post-transcriptional modulation of Bmal1 and its oscillatory regulation in molecular feedback loops mediating SCN circadian function.
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spelling doaj.art-521d4df1d620491cac92304e977fb5a52022-12-22T00:50:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6530010.1371/journal.pone.0065300Role of miR-142-3p in the post-transcriptional regulation of the clock gene Bmal1 in the mouse SCN.Vikram R ShendeNichole NeuendorffDavid J EarnestMicroRNAs (miRNAs) are small non-coding RNAs that function as post-transcriptional modulators by regulating stability or translation of target mRNAs. Recent studies have implicated miRNAs in the regulation of mammalian circadian rhythms. To explore the role of miRNAs in the post-transcriptional modulation of core clock genes in the master circadian pacemaker, we examined miR-142-3p for evidence of circadian expression in the suprachiasmatic nuclei (SCN), regulation of its putative clock gene target Bmal1 via specific binding sites in the 3' UTR and overexpression-induced changes in the circadian rhythm of BMAL1 protein levels in SCN cells. In mice exposed to constant darkness (DD), miR-142-3p levels in the SCN were characterized by circadian rhythmicity with peak expression during early subjective day at CT 3. Mutagenesis studies indicate that two independent miRNA recognition elements located at nucleotides 1-7 and 335-357 contribute equally to miR-142-3p-induced repression of luciferase-reported Bmal1 3' UTR activity. Importantly, overexpression of miR-142-3p in immortalized SCN cells abolished circadian variation in endogenous BMAL1 protein levels in vitro. Collectively, our results suggest that miR-142-3p may play a role in the post-transcriptional modulation of Bmal1 and its oscillatory regulation in molecular feedback loops mediating SCN circadian function.http://europepmc.org/articles/PMC3673942?pdf=render
spellingShingle Vikram R Shende
Nichole Neuendorff
David J Earnest
Role of miR-142-3p in the post-transcriptional regulation of the clock gene Bmal1 in the mouse SCN.
PLoS ONE
title Role of miR-142-3p in the post-transcriptional regulation of the clock gene Bmal1 in the mouse SCN.
title_full Role of miR-142-3p in the post-transcriptional regulation of the clock gene Bmal1 in the mouse SCN.
title_fullStr Role of miR-142-3p in the post-transcriptional regulation of the clock gene Bmal1 in the mouse SCN.
title_full_unstemmed Role of miR-142-3p in the post-transcriptional regulation of the clock gene Bmal1 in the mouse SCN.
title_short Role of miR-142-3p in the post-transcriptional regulation of the clock gene Bmal1 in the mouse SCN.
title_sort role of mir 142 3p in the post transcriptional regulation of the clock gene bmal1 in the mouse scn
url http://europepmc.org/articles/PMC3673942?pdf=render
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