title: Quantifying the strength of miRNA-target interactions.
abstract: We quantify the strength of miRNA-target interactions with MIRZA, a recently introduced biophysical model. We show that computationally predicted energies of interaction correlate strongly with the energies of interaction estimated from biochemical measurements of Michaelis-Menten constants. We further show that the accuracy of the MIRZA model can be improved taking into account recently emerged experimental data types. In particular, we use chimeric miRNA-mRNA sequences to infer a MIRZA-CHIMERA model and we provide a framework for inferring a similar model from measurements of rate constants of miRNA-mRNA interaction in the context of Argonaute proteins. Finally, based on a simple model of miRNA-based regulation, we discuss the importance of interaction energy and its variability between targets for the modulation of miRNA target expression in vivo.
authors.affiliation: Biozentrum, University of Basel and Swiss Institute of Bioinformatics, Klingelbergstrasse 50-70, 4056 Basel, Switzerland.
authors.forename: Jeremie
authors.initials: J
authors.lastname: Breda
authors.affiliation: Biozentrum, University of Basel and Swiss Institute of Bioinformatics, Klingelbergstrasse 50-70, 4056 Basel, Switzerland.
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Rzepiela
authors.affiliation: Biozentrum, University of Basel and Swiss Institute of Bioinformatics, Klingelbergstrasse 50-70, 4056 Basel, Switzerland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Gumienny
authors.affiliation: Biozentrum, University of Basel and Swiss Institute of Bioinformatics, Klingelbergstrasse 50-70, 4056 Basel, Switzerland.
authors.forename: Erik
authors.initials: E
authors.lastname: van Nimwegen
authors.affiliation: Biozentrum, University of Basel and Swiss Institute of Bioinformatics, Klingelbergstrasse 50-70, 4056 Basel, Switzerland. Electronic address: mihaela.zavolan@unibas.ch.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Zavolan
mesh_terms: D001665:Binding Sites / Q000502:physiology; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D017433:Protein Structure, Secondary
chemical_list: D035683:MicroRNAs
keywords: CLASH; CLIP; MIRZA; Non-canonical miRNA binding; miRNA; miRNA target prediction