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Figure 6 | BMC Systems Biology

Figure 6

From: Gene autoregulation via intronic microRNAs and its functions

Figure 6

Map of functions for an intronic miRNA-mediated self-loop. (A) An ON-state of host gene expression is defined by full promoter induction (〈q〉/h r 1), and a sufficiently strong miRNA repression (〈p〉/〈p0〉 < 0.5) can keep it robust in presence of temporary drops in the activator concentration. In the strong repression regime (〈p〉/〈p0 1) adaptation can be observed, and for almost linear transcriptional activation (〈q〉/h r 1) the host gene response can show an adaptive dynamics following Weber’s law. Fluctuations can propagate from the upstream TF more efficiently if the target promoter is highly sensitive to changes in TF level (〈q〉/h r ≈ 1), thus in this parameter region noise buffering is more relevant, with a maximum in efficiency for intermediate repression (〈p〉/〈p0〉 ≈ 0.3). (B) A zoom on the strong repression region shows a transition between different dynamics. A step input can induce a fast transition of the host gene expression between two distinct steady states, but increasing further the repression the two steady states become progressively closer, up to their overlap when adaptation and Weber’s law are implemented. (C) The dynamics is strongly influenced by the relative stability of miRNAs and mRNAs. A short mRNA lifetime is a condition for Weber’s law implementation and contributes to the fast switch-on of the host gene expression. On the other hand, the delay in the switch-off dynamics is larger for short-living miRNAs. In the intermediate region, where the two half-lives are comparable, the trade-off between the two dynamical properties makes the highly-expressed state of the host gene robust with respect to fluctuations in the activator.

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