On the functional properties of microRNA-mediated feed forward loops

TL;DR

This paper explores the functional properties of microRNA-mediated feed-forward loops in genomic regulatory networks, revealing enhanced properties and correlations that suggest specific regulatory preferences.

Contribution

It introduces an analysis of microRNA-based FFLs, extending previous work on transcription factor-based FFLs, and identifies correlations in the D. melanogaster network.

Findings

Enhanced FFL properties with microRNA mediation

Significant correlations between transcription factor and microRNA binding sites

Model suggests transcription factors influence FFL preferences

Abstract

Motivation: Recent studies of genomic-scale regulatory networks suggested that a feed-forward loop (FFL) circuitry is a key component of many such networks. This led to a study of the functional properties of different FFL types, where the regulatory elements are transcription factors. Results: Here we investigate these properties when the mediating regulatory element of the loop is a microRNA. We find that many of the FFL properties are enhanced within this setup. We then proceed to identify all such FFLs in the D. Melanogaster regulatory network. We observe that in FFLs rooted at the same transcription factor there are significant correlations between the number of predicted binding sites for the transcription factor and for the microRNA. Conclusions: Based on a modeling approach we suggest that these correlations may be an outcome of the type of FFL preferred by the transcription factor. This may help elucidate the type of regulation the TF confers.