Probing the Limits to MicroRNA-Mediated Control of Gene Expression

PLoS Comput Biol. 2016 Jan 26;12(1):e1004715. doi: 10.1371/journal.pcbi.1004715. eCollection 2016 Jan.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Computational Biology / methods*
  • Gene Expression Regulation / genetics*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Models, Genetic*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • MicroRNAs
  • Transcription Factors

Grants and funding

This work was supported by Marie Curie Action Initial Training Networks NETworks Across DISciplines, grant agreement n 290038 of the European Union Seventh Framework Programme 2007-2013. www.netadis.eu. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.