Quantifying the strength of miRNA-target interactions

Jeremie Breda; Andrzej J Rzepiela; Rafal Gumienny; Erik van Nimwegen; Mihaela Zavolan

doi:10.1016/j.ymeth.2015.04.012

Quantifying the strength of miRNA-target interactions

Methods. 2015 Sep 1:85:90-99. doi: 10.1016/j.ymeth.2015.04.012. Epub 2015 Apr 16.

Authors

Jeremie Breda¹, Andrzej J Rzepiela¹, Rafal Gumienny¹, Erik van Nimwegen¹, Mihaela Zavolan²

Affiliations

¹ Biozentrum, University of Basel and Swiss Institute of Bioinformatics, Klingelbergstrasse 50-70, 4056 Basel, Switzerland.
² Biozentrum, University of Basel and Swiss Institute of Bioinformatics, Klingelbergstrasse 50-70, 4056 Basel, Switzerland. Electronic address: mihaela.zavolan@unibas.ch.

PMID: 25892562
DOI: 10.1016/j.ymeth.2015.04.012

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.

Keywords: CLASH; CLIP; MIRZA; Non-canonical miRNA binding; miRNA; miRNA target prediction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites / physiology
Gene Targeting / methods*
Humans
MicroRNAs / chemistry*
MicroRNAs / metabolism*
Models, Molecular*
Protein Structure, Secondary

Substances

MicroRNAs