Figure 5

Proposed “hyper-regulation” of gene expression by miRNAs. The figure shows the role of miRNAs in the complex transcriptional network (blue arrow). By regulating (blue arrow) the expression of genes that are involved in the regulation of the expression of genes, a miRNA-dependent regulatory mechanism of gene regulation is formed on top of the miRNA-independent regulation of gene expression (green arrow). By this regulatory mechanism, proposed as “hyper-regulation” of gene expression (blue arrow), miRNAs interfere with the whole transcriptome mainly including intranuclear mechanisms besides the well-known extranuclear (red arrow) mechanisms. Hyper-regulation accommodates observations of global gene down-regulation in the absence of miRNAs [47] which downregulate gene product that reduce gene transcription such as DNA methyltransferases (Additional file 2: Table S1. RegulatedGenes_vs_miRNAs_Matrix.xlsx).