ceRNA crosstalk stabilizes protein expression and affects the correlation pattern of interacting proteins

TL;DR

This paper shows through simulations and modeling that miRNA-mediated crosstalk between mRNAs stabilizes protein levels and alters correlation patterns of interacting proteins, revealing a new layer of gene regulation.

Contribution

It introduces a novel concept that miRNA-induced competition causes widespread protein stabilization and changes in protein correlation patterns, extending beyond traditional noise buffering.

Findings

miRNA crosstalk stabilizes protein levels across gene expression ranges

It changes correlation patterns of co-regulated proteins from negative to positive

RNA crosstalk signatures can be detected in standard cellular conditions

Abstract

Gene expression is a noisy process and several mechanisms, both transcriptional and posttranscriptional, can stabilize protein levels in cells. Much work has focused on the role of miRNAs, showing in particular that miRNA-mediated regulation can buffer expression noise for lowly expressed genes. Here, using in silico simulations and mathematical modeling, we demonstrate that miRNAs can exert a much broader influence on protein levels by orchestrating competition-induced crosstalk between mRNAs. Most notably, we find that miRNA-mediated cross-talk (i) can stabilize protein levels across the full range of gene expression rates, and (ii) modifies the correlation pattern of co-regulated interacting proteins, changing the sign of correlations from negative to positive. The latter feature may constitute a potentially robust signature of the existence of RNA crosstalk induced by endogenous competition for miRNAs in standard cellular conditions.