Intronic microRNAs support their host genes by mediating synergistic and antagonistic regulatory effects

MicroRNA-mediated control of gene expression via translational inhibition has substantial impact on cellular regulatory mechanisms. About 37% of mammalian microRNAs appear to be located within introns of protein coding genes, linking their expression to the promoter-driven regulation of the host gene. In our study we investigate this linkage towards a relationship beyond transcriptional co-regulation.

Using measures based on both annotation and experimental data, we show that intronic microRNAs tend to support their host genes by regulation of target gene expression with significantly correlated expression patterns. We used expression data of three differentiating cell types and compared gene expression profiles of host and target genes. Many microRNA target genes show expression patterns significantly correlated with the expressions of the microRNA host genes. By calculating functional similarities between host and predicted microRNA target genes based on GO annotations, we confirm that many microRNAs link host and target gene activity in an either synergistic or antagonistic manner.

These two regulatory effects may result from fine tuning of target gene expression functionally related to the host or knock-down of remaining opponent target gene expression. This finding allows to extend the common practice of mapping large scale gene expression data to protein associated genes with functionality of co-expressed intronic microRNAs.