量化微小RNA与靶标的相互作用强度。

Quantifying the strength of miRNA-target interactions.

作者信息

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

机构信息

Biozentrum, University of Basel and Swiss Institute of Bioinformatics, Klingelbergstrasse 50-70, 4056 Basel, Switzerland.

出版信息

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

DOI:10.1016/j.ymeth.2015.04.012

PMID:25892562

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.

摘要

我们使用最近推出的生物物理模型MIRZA对微小RNA（miRNA）与靶标的相互作用强度进行了量化。我们发现，通过计算预测的相互作用能量与根据米氏常数的生化测量估算出的相互作用能量密切相关。我们进一步表明，考虑到最近出现的实验数据类型，可以提高MIRZA模型的准确性。具体而言，我们使用嵌合miRNA-信使核糖核酸（mRNA）序列来推导MIRZA-CHIMERA模型，并提供了一个框架，用于从在AGO蛋白背景下miRNA-mRNA相互作用速率常数的测量中推导类似模型。最后，基于一个简单的基于miRNA的调控模型，我们讨论了相互作用能量及其在不同靶标之间的变异性对于体内miRNA靶标表达调控的重要性。