Probing the limits to microRNA-mediated control of gene expression

TL;DR

This paper quantitatively analyzes the capacity and limitations of microRNA-mediated gene regulation, revealing conditions under which it outperforms transcriptional control and its role in noise buffering and fine-tuning gene expression.

Contribution

It introduces a quantitative framework for understanding miRNA regulation as an information channel, identifying scenarios where it surpasses direct transcriptional control.

Findings

Post-transcriptional miRNA channels can outperform transcriptional control under certain mechanisms.

Large populations of weakly interacting miRNAs reduce noise, enhancing information processing.

miRNA regulation can serve as a noise buffer and a fine-tuning mechanism in gene expression.

Abstract

According to the `ceRNA hypothesis', microRNAs (miRNAs) may act as mediators of an effective positive interaction between long coding or non-coding RNA molecules, carrying significant potential implications for a variety of biological processes. Here, inspired by recent work providing a quantitative description of small regulatory elements as information-conveying channels, we characterize the effectiveness of miRNA-mediated regulation in terms of the optimal information flow achievable between modulator (transcription factors) and target nodes (long RNAs). Our findings show that, while a sufficiently large degree of target derepression is needed to activate miRNA-mediated transmission, (a) in case of differential mechanisms of complex processing and/or transcriptional capabilities, regulation by a post-transcriptional miRNA-channel can outperform that achieved through direct transcriptional control; moreover, (b) in the presence of large populations of weakly interacting miRNA molecules the extra noise coming from titration disappears, allowing the miRNA-channel to process information as effectively as the direct channel. These observations establish the limits of miRNA-mediated post-transcriptional cross-talk and suggest that, besides providing a degree of noise buffering, this type of control may be effectively employed in cells both as a failsafe mechanism and as a preferential fine tuner of gene expression, pointing to the specific situations in which each of these functionalities is maximized.