title: MiRBooking simulates the stoichiometric mode of action of microRNAs.
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.
authors.affiliation: Institute for Research in Immunology and Cancer, and Department of Computer Science and Operations Research, Université de Montréal, PO Box 6128, Downtown Station, Montréal, Québec H3C 3J7, Canada.
authors.forename: Nathanaël
authors.initials: N
authors.lastname: Weill
authors.affiliation: Institute for Research in Immunology and Cancer, and Department of Computer Science and Operations Research, Université de Montréal, PO Box 6128, Downtown Station, Montréal, Québec H3C 3J7, Canada.
authors.forename: Véronique
authors.initials: V
authors.lastname: Lisi
authors.affiliation: Institute for Research in Immunology and Cancer, and Department of Computer Science and Operations Research, Université de Montréal, PO Box 6128, Downtown Station, Montréal, Québec H3C 3J7, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Scott
authors.affiliation: Institute for Research in Immunology and Cancer, and Department of Computer Science and Operations Research, Université de Montréal, PO Box 6128, Downtown Station, Montréal, Québec H3C 3J7, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Dallaire
authors.affiliation: Institute for Research in Immunology and Cancer, and Department of Computer Science and Operations Research, Université de Montréal, PO Box 6128, Downtown Station, Montréal, Québec H3C 3J7, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Pelloux
authors.affiliation: Institute for Research in Immunology and Cancer, and Department of Computer Science and Operations Research, Université de Montréal, PO Box 6128, Downtown Station, Montréal, Québec H3C 3J7, Canada major@iro.umontreal.ca.
authors.forename: François
authors.initials: F
authors.lastname: Major
mesh_terms: D000465:Algorithms; D002460:Cell Line; D020868:Gene Silencing; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger