MicroRNAs as a selective channel of communication between competing RNAs: a steady-state theory

TL;DR

This paper develops a steady-state theoretical model to understand how competition for microRNAs leads to selective interactions among RNAs, influencing post-transcriptional regulation and gene expression.

Contribution

It introduces a minimal steady-state model that characterizes the emergence and nature of ceRNA interactions based on binding energies and repression mechanisms.

Findings

Interactions depend on repression levels and can be symmetrical or asymmetrical.

Selective and noise-limited interactions can emerge in specific parameter ranges.

Correlations among RNAs can arise from transcriptional fluctuations without miRNA cross-talk.

Abstract

It has recently been suggested that the competition for a finite pool of microRNAs (miRNA) gives rise to effective interactions among their common targets (competing endogenous RNAs or ceRNAs) that could prove to be crucial for post-transcriptional regulation (PTR). We have studied a minimal model of PTR where the emergence and the nature of such interactions can be characterized in detail at steady state. Sensitivity analysis shows that binding free energies and repression mechanisms are the key ingredients for the cross-talk between ceRNAs to arise. Interactions emerge in specific ranges of repression values, can be symmetrical (one ceRNA influences another and vice-versa) or asymmetrical (one ceRNA influences another but not the reverse) and may be highly selective, while possibly limited by noise. In addition, we show that non-trivial correlations among ceRNAs can emerge in experimental readouts due to transcriptional fluctuations even in absence of miRNA-mediated cross-talk.