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MiRBooking simulates the stoichiometric mode of action of microRNAs.

Authors :
Weill N
Lisi V
Scott N
Dallaire P
Pelloux J
Major F
Source :
Nucleic acids research [Nucleic Acids Res] 2015 Aug 18; Vol. 43 (14), pp. 6730-8. Date of Electronic Publication: 2015 Jun 18.
Publication Year :
2015

Abstract

In eucaryotes, gene expression is regulated by microRNAs (miRNAs) which bind to messenger RNAs (mRNAs) and interfere with their translation into proteins, either by promoting their degradation or inducing their repression. We study the effect of miRNA interference on each gene using experimental methods, such as microarrays and RNA-seq at the mRNA level, or luciferase reporter assays and variations of SILAC at the protein level. Alternatively, computational predictions would provide clear benefits. However, no algorithm toward this task has ever been proposed. Here, we introduce a new algorithm to predict genome-wide expression data from initial transcriptome abundance. The algorithm simulates the miRNA and mRNA hybridization competition that occurs in given cellular conditions, and derives the whole set of miRNA::mRNA interactions at equilibrium (microtargetome). Interestingly, solving the competition improves the accuracy of miRNA target predictions. Furthermore, this model implements a previously reported and fundamental property of the microtargetome: the binding between a miRNA and a mRNA depends on their sequence complementarity, but also on the abundance of all RNAs expressed in the cell, i.e. the stoichiometry of all the miRNA sites and all the miRNAs given their respective abundance. This model generalizes the miRNA-induced synchronistic silencing previously observed, and described as sponges and competitive endogenous RNAs.<br /> (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Details

Language :
English
ISSN :
1362-4962
Volume :
43
Issue :
14
Database :
MEDLINE
Journal :
Nucleic acids research
Publication Type :
Academic Journal
Accession number :
26089388
Full Text :
https://doi.org/10.1093/nar/gkv619