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...
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Public Library of Science (PLoS)
2011-01-01
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Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3142187?pdf=render |
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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. |
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institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
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publishDate | 2011-01-01 |
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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 |
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