Quantitative study of crossregulation, noise and synchronization between microRNA targets in single cells

TL;DR

This study investigates the complex interactions, noise, and synchronization between microRNA targets at the single-cell level, revealing conditions for target crosstalk, population coexistence, and correlations through quantitative measurements and stochastic modeling.

Contribution

It provides the first detailed single-cell analysis of microRNA target crosstalk dynamics under physiological conditions, supported by a stochastic molecular titration model.

Findings

Crosstalk occurs only under specific stoichiometric conditions.

A trade-off in regulatory elements can lead to distinct cell populations.

Strong correlations between targets are observed in single cells.

Abstract

Recent studies reported complex post-transcriptional interplay among targets of a common pool of microRNAs, a class of small non-coding downregulators of gene expression. Behaving as microRNA-sponges, distinct RNA species may compete for binding to microRNAs and coregulate each other in a dose-dependent manner. Although previous studies in cell populations showed competition in vitro, the detailed dynamical aspects of this process, most importantly in physiological conditions, remains unclear. We address this point by monitoring protein expression of two targets of a common miRNA with quantitative single-cell measurements. In agreement with a detailed stochastic model of molecular titration, we observed that: (i) crosstalk between targets is possible only in particular stoichiometric conditions, (ii) a trade-off on the number of microRNA regulatory elements may induce the coexistence of two distinct cell populations, (iii) strong inter-targets correlations can be observed. This phenomenology is compatible with a small amount of mRNA target molecules per cell of the order of 10-100.