Global Analyses of the Effect of Different Cellular Contexts on MicroRNA Targeting
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Bartel_Global analyses.pdf
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3.07 MB
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Author(s)
Nam, Jin-Wu
Rissland, Olivia S.
Abreu-Goodger, Cei
Jan, Calvin H.
Agarwal, Vikram
Yildirim, Muhammed A.
Rodriguez, Antony
Koppstein, David Neal Pira
Bartel, David
Rissland, Olivia S.
Date Issued
March 2014
Journal
Molecular Cell
Publisher
Elsevier
Citation
Nam, Jin-Wu, Olivia S. Rissland, David Koppstein, Cei Abreu-Goodger, Calvin H. Jan, Vikram Agarwal, Muhammed A. Yildirim, Antony Rodriguez, and David P. Bartel. “Global Analyses of the Effect of Different Cellular Contexts on MicroRNA Targeting.” Molecular Cell 53, no. 6 (March 2014): 1031–1043. © 2014 Elsevier Inc.
Version
Final published version
Abstract
MicroRNA (miRNA) regulation clearly impacts animal development, but the extent to which development—with its resulting diversity of cellular contexts—impacts miRNA regulation is unclear. Here, we compared cohorts of genes repressed by the same miRNAs in different cell lines and tissues and found that target repertoires were largely unaffected, with secondary effects explaining most of the differential responses detected. Outliers resulting from differential direct targeting were often attributable to alternative 3′ UTR isoform usage that modulated the presence of miRNA sites. More inclusive examination of alternative 3′ UTR isoforms revealed that they influence ~10% of predicted targets when comparing any two cell types. Indeed, considering alternative 3′ UTR isoform usage improved prediction of targeting efficacy significantly beyond the improvements observed when considering constitutive isoform usage. Thus, although miRNA targeting is remarkably consistent in different cell types, considering the 3′ UTR landscape helps predict targeting efficacy and explain differential regulation that is observed.
MIT Department
Massachusetts Institute of Technology. Computational and Systems Biology Program
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.molcel.2014.02.013
