mRNA Destabilization Is the Dominant Effect of Mammalian MicroRNAs by the Time Substantial Repression Ensues

MicroRNAs (miRNAs) regulate target mRNAs through a combination of translational repression and mRNA destabilization, with mRNA destabilization dominating at steady state in the few contexts examined globally. Here, we extend the global steady-state measurements to additional mammalian contexts and f...

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Main Authors: Eichhorn, Stephen W., Guo, Huili, McGeary, Sean E., Rodriguez-Mias, Ricard A., Shin, Chanseok, Baek, Daehyun, Hsu, Shu-hao, Ghoshal, Kalpana, Villén, Judit, Bartel, David P.
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2016
Subjects:
Online Access:https://hdl.handle.net/10356/83818
http://hdl.handle.net/10220/41504
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-838182022-02-16T16:31:26Z mRNA Destabilization Is the Dominant Effect of Mammalian MicroRNAs by the Time Substantial Repression Ensues Eichhorn, Stephen W. Guo, Huili McGeary, Sean E. Rodriguez-Mias, Ricard A. Shin, Chanseok Baek, Daehyun Hsu, Shu-hao Ghoshal, Kalpana Villén, Judit Bartel, David P. Lee Kong Chian School of Medicine (LKCMedicine) RNA degradation microRNA MicroRNAs (miRNAs) regulate target mRNAs through a combination of translational repression and mRNA destabilization, with mRNA destabilization dominating at steady state in the few contexts examined globally. Here, we extend the global steady-state measurements to additional mammalian contexts and find that regardless of the miRNA, cell type, growth condition, or translational state, mRNA destabilization explains most (66%–>90%) miRNA-mediated repression. We also determine the relative dynamics of translational repression and mRNA destabilization for endogenous mRNAs as a miRNA is induced. Although translational repression occurs rapidly, its effect is relatively weak, such that by the time consequential repression ensues, the effect of mRNA destabilization dominates. These results imply that consequential miRNA-mediated repression is largely irreversible and provide other insights into the nature of miRNA-mediated regulation. They also simplify future studies, dramatically extending the known contexts and time points for which monitoring mRNA changes captures most of the direct miRNA effects. ASTAR (Agency for Sci., Tech. and Research, S’pore) 2016-09-28T04:04:52Z 2019-12-06T15:32:41Z 2016-09-28T04:04:52Z 2019-12-06T15:32:41Z 2014 Journal Article Eichhorn, S. W., Guo, H., McGeary, S. E., Rodriguez-Mias, R. A., Shin, C., Baek, D., et al. (2014). mRNA Destabilization Is the Dominant Effect of Mammalian MicroRNAs by the Time Substantial Repression Ensues. Molecular Cell, 56(1), 104-115. 1097-2765 https://hdl.handle.net/10356/83818 http://hdl.handle.net/10220/41504 10.1016/j.molcel.2014.08.028 25263593 en Molecular Cell © 2014 Elsevier Inc.
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic RNA degradation
microRNA
spellingShingle RNA degradation
microRNA
Eichhorn, Stephen W.
Guo, Huili
McGeary, Sean E.
Rodriguez-Mias, Ricard A.
Shin, Chanseok
Baek, Daehyun
Hsu, Shu-hao
Ghoshal, Kalpana
Villén, Judit
Bartel, David P.
mRNA Destabilization Is the Dominant Effect of Mammalian MicroRNAs by the Time Substantial Repression Ensues
description MicroRNAs (miRNAs) regulate target mRNAs through a combination of translational repression and mRNA destabilization, with mRNA destabilization dominating at steady state in the few contexts examined globally. Here, we extend the global steady-state measurements to additional mammalian contexts and find that regardless of the miRNA, cell type, growth condition, or translational state, mRNA destabilization explains most (66%–>90%) miRNA-mediated repression. We also determine the relative dynamics of translational repression and mRNA destabilization for endogenous mRNAs as a miRNA is induced. Although translational repression occurs rapidly, its effect is relatively weak, such that by the time consequential repression ensues, the effect of mRNA destabilization dominates. These results imply that consequential miRNA-mediated repression is largely irreversible and provide other insights into the nature of miRNA-mediated regulation. They also simplify future studies, dramatically extending the known contexts and time points for which monitoring mRNA changes captures most of the direct miRNA effects.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Eichhorn, Stephen W.
Guo, Huili
McGeary, Sean E.
Rodriguez-Mias, Ricard A.
Shin, Chanseok
Baek, Daehyun
Hsu, Shu-hao
Ghoshal, Kalpana
Villén, Judit
Bartel, David P.
format Article
author Eichhorn, Stephen W.
Guo, Huili
McGeary, Sean E.
Rodriguez-Mias, Ricard A.
Shin, Chanseok
Baek, Daehyun
Hsu, Shu-hao
Ghoshal, Kalpana
Villén, Judit
Bartel, David P.
author_sort Eichhorn, Stephen W.
title mRNA Destabilization Is the Dominant Effect of Mammalian MicroRNAs by the Time Substantial Repression Ensues
title_short mRNA Destabilization Is the Dominant Effect of Mammalian MicroRNAs by the Time Substantial Repression Ensues
title_full mRNA Destabilization Is the Dominant Effect of Mammalian MicroRNAs by the Time Substantial Repression Ensues
title_fullStr mRNA Destabilization Is the Dominant Effect of Mammalian MicroRNAs by the Time Substantial Repression Ensues
title_full_unstemmed mRNA Destabilization Is the Dominant Effect of Mammalian MicroRNAs by the Time Substantial Repression Ensues
title_sort mrna destabilization is the dominant effect of mammalian micrornas by the time substantial repression ensues
publishDate 2016
url https://hdl.handle.net/10356/83818
http://hdl.handle.net/10220/41504
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