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...
Main Authors: | , , |
---|---|
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 |
_version_ | 1818179604783824896 |
---|---|
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. |
first_indexed | 2024-12-11T21:06:31Z |
format | Article |
id | doaj.art-521d4df1d620491cac92304e977fb5a5 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-11T21:06:31Z |
publishDate | 2013-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
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 |
work_keys_str_mv | AT vikramrshende roleofmir1423pintheposttranscriptionalregulationoftheclockgenebmal1inthemousescn AT nicholeneuendorff roleofmir1423pintheposttranscriptionalregulationoftheclockgenebmal1inthemousescn AT davidjearnest roleofmir1423pintheposttranscriptionalregulationoftheclockgenebmal1inthemousescn |