Inter- and Intra-Combinatorial Regulation by Transcription Factors and MicroRNAs

摘要

MicroRNAs (miRNAs) are a class of small RNAs whose functions remain unclear. Here, we studied the nature of coordination among transcriptional and miRNA regulatory layers by assessment of regulatory "interactions" among the sets of predicted targets of miRNAs and of transcription factors (TFs). We found that regulation by TF pairs and miRNA pairs is more abundant than the regulation by TF-miRNA pairs, perhaps due to the higher probability of evolutionary duplication events of shorter DNA sequences. Application of significance measures for evaluating the degree of interaction between regulators shows that strongly interacting regulatory pairs tend to include regulators with large numbers of genes. Therefore, we introduced a Bayesian score that combines the significance and strength of an interaction. We found that strongly interacting TF-miRNA pairs are more likely to form feed forward loops. This may be attributed to processes that prevent waste of resources or accelerate mRNA degradation.