Figure 3.

Mechanisms of interaction between miRNAs and PRMTs.

Multiple mechanisms of interaction between miRNAs and PRMTs including, a. Regulation of miRNAs by PRMTs in which histones in the promoter regions of miRNAs are methylated such as H3R8me2s, H4R3me2s, etc. resulting in transcriptional silencing of these miRNAs; b. Regulation of PRMTs by miRNAs involves targeting of 3ʹ-UTRs of PRMTs for degradation, ultimately blocking translation of the PRMT protein; c. Example of the reciprocal interplay between PRMTs and miRNAs at multiple levels in normal and cancerous states: during physiologically normal conditions, (I) miRNAs target PRMTs at their 3ʹ-UTRs for degradation, keeping their levels in check. However, in cancer, decrease of miRNA levels via epigenetic mechanisms including (II) PRMT-catalyzed methylation of histones at the promoters of miRNAs can act to silence these same miRNAs. (III) Additionally, PRMTs can methylate proteins of the miRNA processing machinery such as Drosha, which results in deregulation of miRNA biogenesis. Furthermore, another level of complexity is introduced when (IV) certain regulatory loops involve other epigenetic components such as HDACs which can form repressive complexes to further suppress miRNA expression. The net effect is upregulation of PRMTs that promote cancer processes.