mRNA Destabilization Is the Dominant Effect of Mammalian MicroRNAs by the Time Substantial Repression Ensues
Name
nihms-626710.pdf
Size
609.95 KB
Format
Adobe PDF
Checksum (MD5)
7fc2bf092f24dc78fb45952e31784d48
Author(s)
Rodriguez-Mias, Ricard A.
Shin, Chanseok
Baek, Daehyun
Hsu, Shu-hao
Ghoshal, Kalpana
Villén, Judit
Eichhorn, Stephen William
Guo, Huili
McGeary, Sean Edward
Bartel, David
Date Issued
September 2014
Journal
Molecular Cell
Publisher
Elsevier BV
Citation
Eichhorn, Stephen W. et al. “mRNA Destabilization Is the Dominant Effect of Mammalian MicroRNAs by the Time Substantial Repression Ensues.” Molecular Cell 56, 1 (October 2014): 104–115 © 2014 Elsevier Inc
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.MOLCEL.2014.08.028
