Gene autoregulation via intronic microRNAs and its functions

Autoregulation via intronic microRNAs is widespread in the human regulatory network, as confirmed by our bioinformatic analysis, and can perform several regulatory tasks despite its simple topology. Our analysis, based on analytical calculations and simulations, indicates that this circuitry alters the dynamics of the host gene expression, can induce complex responses implementing adaptation and Weber’s law, and efficiently filters fluctuations propagating from the upstream network to the host gene. A fine-tuning of the circuit parameters can optimize each of these functions. Interestingly, they are all related to gene expression homeostasis, in agreement with the increasing evidence suggesting a role of microRNA regulation in conferring robustness to biological processes. In addition to model analysis, we present a list of bioinformatically predicted candidate circuits in human for future experimental tests.The results presented here suggest a potentially relevant functional role for negative self-regulation via intronic microRNAs, in particular as a homeostatic control mechanism of gene expression. Moreover, the map of circuit functions in terms of experimentally measurable parameters, resulting from our analysis, can be a useful guideline for possible applications in synthetic biology.microRNAs (miRNAs) are small (about 22 nucleotides) single-strand RNAs able to interfere post-transcriptionally with the protein production of their targets. Targeting a vast proportion of protein-coding genes [1-3], miRNA-mediated regulation composes an important layer in gene regulatory networks. The implication of miRNAs in several core cellular processes [4-7] as well as in many human diseases [8,9] further confirms their biological importance.Approximately half of the miRNA genes can be found in intergenic regions (between genes), whereas the intragenic miRNAs (inside genes) are predominantly located inside introns and usually oriented on the same DNA strand of the host gene [1