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

Sci Rep. 2017 Mar 7:7:43673. doi: 10.1038/srep43673.

Abstract

Gene expression is a noisy process and several mechanisms, both transcriptional and post-transcriptional, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Epistasis, Genetic*
  • Gene Expression Regulation*
  • Gene Regulatory Networks
  • MicroRNAs / genetics
  • Models, Biological
  • Protein Binding
  • Protein Stability
  • RNA / genetics*
  • RNA Interference*
  • Transcription, Genetic

Substances

  • Carrier Proteins
  • MicroRNAs
  • RNA