Two examples of mixed regulatory circuits, each containing a miRNA (oblate spheroid), linked to TFs (trapezoids) and coding gene targets (rectangles), all of which changed their expression in response to transient ischemia-reperfusion injury in the retina. The numbers and bold arrows represent fold change relative to sham control animals and up- /downregulation (resp.) of the miRNAs, TFs, and protein coding genes implicated in the mixed regulatory circuits. (a) Direct and indirect downregulation of two coding genes by the same miRNA (rno-miR-101a). At 24 h IR period, rno-miR-101a targets the protein coding genes Gria4 (glutamate receptor) and Nefl (neurofilament) directly. At the same time, rno-miR-101a can control these genes indirectly by targeting the TF Nptx1, which in turn targets Gria4 and Nefl. (b) miRNA targets several TFs which act together to coordinate the reduced expression of a single gene. At 24 h IR period, rno-miR-99a targets the protein coding gene Icam1 (adhesion molecule) directly. At the same time, rno-miR-99a can control this gene indirectly by targeting 3TFs (Arpc1b, Cebpb, and Stat3), which in turn target Icam1.
