MicroRNAs as a Selective Channel of Communication between Competing RNAs: a Steady-State Theory

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 posttranscriptional regulation. We have studied a minimal model of posttranscriptional regulation 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 nontrivial correlations among ceRNAs can emerge in experimental readouts due to transcriptional fluctuations even in the absence of miRNA-mediated cross-talk.