Quantitative prediction of miRNA-mRNA interaction based on equilibrium concentrations

Ragan, Chikako, Zuker, Michael and Ragan, Mark A. (2011) Quantitative prediction of miRNA-mRNA interaction based on equilibrium concentrations. PLoS Computational Biology, 7 2: e1001090-1-e1001090-11. doi:10.1371/journal.pcbi.1001090


Author Ragan, Chikako
Zuker, Michael
Ragan, Mark A.
Title Quantitative prediction of miRNA-mRNA interaction based on equilibrium concentrations
Journal name PLoS Computational Biology   Check publisher's open access policy
ISSN 1553-734X
1553-7358
Publication date 2011-02-24
Sub-type Article (original research)
DOI 10.1371/journal.pcbi.1001090
Open Access Status DOI
Volume 7
Issue 2
Start page e1001090-1
End page e1001090-11
Total pages 11
Place of publication La Jolla, CA, U.S.A.
Publisher Public Library of Science
Collection year 2012
Language eng
Formatted abstract
MicroRNAs (miRNAs) suppress gene expression by forming a duplex with a target messenger RNA (mRNA), blocking translation or initiating cleavage. Computational approaches have proven valuable for predicting which mRNAs can be targeted by a given miRNA, but currently available prediction methods do not address the extent of duplex formation under physiological conditions. Some miRNAs can at low concentrations bind to target mRNAs, whereas others are unlikely to bind within a physiologically relevant concentration range. Here we present a novel approach in which we find potential target sites on mRNA that minimize the calculated free energy of duplex formation, compute the free energy change involved in unfolding these sites, and use these energies to estimate the extent of duplex formation at specified initial concentrations of both species. We compare our predictions to experimentally confirmed miRNA-mRNA interactions (and non-interactions) in Drosophila melanogaster and in human. Although our method does not predict whether the targeted mRNA is degraded and/or its translation to protein inhibited, our quantitative estimates generally track experimentally supported results, indicating that this approach can be used to predict whether an interaction occurs at specified concentrations. Our approach offers a more-quantitative understanding of post-translational regulation in different cell types, tissues, and developmental conditions.

Author Summary: MicroRNAs (miRNAs) are small RNA molecules that regulate post-transcriptional gene expression by binding messenger RNAs (mRNAs), blocking their role in translation or marking them for degradation. To date, computational methods for predicting mRNA targets have assumed an all-or-nothing mode of miRNA-mRNA interaction. Here we introduce a computational approach that predicts the degree of interaction, taking into account initial miRNA and mRNA concentrations. Using this approach, we can predict whether specified interactions are likely to be functionally relevant within physiologically relevant concentration ranges.
Copyright: © 2011 Ragan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keyword MicroRNA target sites
Secondary structure
Expression
Recognition
Protein
Thermodynamics
Hybridization
Parameters
Elegans
Binding
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article #e1001090.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Sun, 13 Mar 2011, 00:05:15 EST