Expression and rhythmic modulation of circulating microRNAs targeting the clock gene Bmal1 in mice.

MicroRNAs (miRNAs) interact with 3' untranslated region (UTR) elements of target genes to regulate mRNA stability or translation and thus play a role in regulating many different biological processes, including circadian rhythms. However, specific miRNAs mediating the regulation of essential cl...

Full description

Bibliographic Details
Main Authors: Vikram R Shende, Marianna M Goldrick, Suchitra Ramani, David J Earnest
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3142187?pdf=render
_version_ 1811194210415542272
author Vikram R Shende
Marianna M Goldrick
Suchitra Ramani
David J Earnest
author_facet Vikram R Shende
Marianna M Goldrick
Suchitra Ramani
David J Earnest
author_sort Vikram R Shende
collection DOAJ
description MicroRNAs (miRNAs) interact with 3' untranslated region (UTR) elements of target genes to regulate mRNA stability or translation and thus play a role in regulating many different biological processes, including circadian rhythms. However, specific miRNAs mediating the regulation of essential clock genes remain largely unknown. Because vesicles containing membrane-bound miRNAs are present in the circulatory system, we examined miRNAs predicted to target the clock gene, Bmal1, for evidence of rhythmic fluctuations in circulating levels and modulatory effects on the 3' UTR activity of Bmal1. A number of miRNAs with Bmal1 as a predicted target were expressed in the serum of mice exposed to LD 12:12 and of these miRNAs, miR-152 and miR-494 but not miR-142-3p were marked by diurnal oscillations with bimodal peaks in expression occurring near the middle of the day and 8 or 12 hr later during the night. Co-transfection of pre-miR over-expression constructs for miR-494 and miR-142-3p in HEK293 cells had significant effects in repressing luciferase-reported Bmal1 3' UTR activity by as much as 60%, suggesting that these miRNAs may function as post-transcriptional modulators of Bmal1. In conjunction with previous studies implicating miRNAs as extracellular regulatory signals, our results suggest that circulating miRNAs may play a role in the regulation of the molecular clockworks in peripheral circadian oscillators.
first_indexed 2024-04-12T00:22:07Z
format Article
id doaj.art-46fef750f1be410899109fbffc3fa102
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-04-12T00:22:07Z
publishDate 2011-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-46fef750f1be410899109fbffc3fa1022022-12-22T03:55:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0167e2258610.1371/journal.pone.0022586Expression and rhythmic modulation of circulating microRNAs targeting the clock gene Bmal1 in mice.Vikram R ShendeMarianna M GoldrickSuchitra RamaniDavid J EarnestMicroRNAs (miRNAs) interact with 3' untranslated region (UTR) elements of target genes to regulate mRNA stability or translation and thus play a role in regulating many different biological processes, including circadian rhythms. However, specific miRNAs mediating the regulation of essential clock genes remain largely unknown. Because vesicles containing membrane-bound miRNAs are present in the circulatory system, we examined miRNAs predicted to target the clock gene, Bmal1, for evidence of rhythmic fluctuations in circulating levels and modulatory effects on the 3' UTR activity of Bmal1. A number of miRNAs with Bmal1 as a predicted target were expressed in the serum of mice exposed to LD 12:12 and of these miRNAs, miR-152 and miR-494 but not miR-142-3p were marked by diurnal oscillations with bimodal peaks in expression occurring near the middle of the day and 8 or 12 hr later during the night. Co-transfection of pre-miR over-expression constructs for miR-494 and miR-142-3p in HEK293 cells had significant effects in repressing luciferase-reported Bmal1 3' UTR activity by as much as 60%, suggesting that these miRNAs may function as post-transcriptional modulators of Bmal1. In conjunction with previous studies implicating miRNAs as extracellular regulatory signals, our results suggest that circulating miRNAs may play a role in the regulation of the molecular clockworks in peripheral circadian oscillators.http://europepmc.org/articles/PMC3142187?pdf=render
spellingShingle Vikram R Shende
Marianna M Goldrick
Suchitra Ramani
David J Earnest
Expression and rhythmic modulation of circulating microRNAs targeting the clock gene Bmal1 in mice.
PLoS ONE
title Expression and rhythmic modulation of circulating microRNAs targeting the clock gene Bmal1 in mice.
title_full Expression and rhythmic modulation of circulating microRNAs targeting the clock gene Bmal1 in mice.
title_fullStr Expression and rhythmic modulation of circulating microRNAs targeting the clock gene Bmal1 in mice.
title_full_unstemmed Expression and rhythmic modulation of circulating microRNAs targeting the clock gene Bmal1 in mice.
title_short Expression and rhythmic modulation of circulating microRNAs targeting the clock gene Bmal1 in mice.
title_sort expression and rhythmic modulation of circulating micrornas targeting the clock gene bmal1 in mice
url http://europepmc.org/articles/PMC3142187?pdf=render
work_keys_str_mv AT vikramrshende expressionandrhythmicmodulationofcirculatingmicrornastargetingtheclockgenebmal1inmice
AT mariannamgoldrick expressionandrhythmicmodulationofcirculatingmicrornastargetingtheclockgenebmal1inmice
AT suchitraramani expressionandrhythmicmodulationofcirculatingmicrornastargetingtheclockgenebmal1inmice
AT davidjearnest expressionandrhythmicmodulationofcirculatingmicrornastargetingtheclockgenebmal1inmice