Combined model extensions 3 and 4: Upregulation of both an ITF and miRNA(s) is required for inhibition of Atf3 mRNA and protein.

<p>(A) The conceptual model of the ITF and miRNA inhibitory pathways for Atf3 transcriptional regulation (dashed lines). Symbols are as for <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003597#pcbi-1003597-g001" target="_blank">Figure 1C</a>. B, C and D, Predicted concentrations of total Atf3 mRNA (i.e. mRNA + miRNA.mRNA complex) (B, blue lines), Atf3 protein (C, green lines) and Egr1 mRNA (D, pink lines) when the rate of degradation of Atf3 mRNA within the miRNA.mRNA complex is the same as for degradation of free Atf3 mRNA (solid line), is increased 2-fold (long dashed lines) or is increased 4-fold (short dashed line). The predicted curves are superimposed on the experimental data (solid black lines, right axes) to which a spline curve was fitted.