MitomiRs, ChloromiRs and Modelling of the microRNA Inhibition
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MitomiRs, ChloromiRs and Modelling of the microRNA Inhibition J. Demongeot • H. Hazgui • S. Bandiera • O. Cohen A. Henrion-Caude
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Received: 24 December 2012 / Accepted: 20 July 2013 Springer Science+Business Media Dordrecht 2013
Abstract MicroRNAs are non-coding parts of nuclear and mitochondrial genomes, preventing the weakest part of the genetic regulatory networks from being expressed and preventing the appearance of a too many attractors in these networks. They have also a great influence on the chromatin clock, which ensures the updating of the genetic regulatory networks. The post-transcriptional inhibitory activity by the microRNAs, which is partly unspecific, is due firstly to their possibly direct negative action during translation by hybridizing tRNAs, especially those inside the mitochondrion, hence slowing mitochondrial respiration, and secondly to their action on a large number of putative m-RNA targets like those involved in immunetworks; We show that the circuits in the core of the interaction graphs are responsible for the small number of dedicated attractors that correspond to genetically controlled functions, partly due to a general filtering by the microRNAs. We analyze this influence as well as their impact on important functions like the control J. Demongeot (&) H. Hazgui O. Cohen AGIM, FRE CNRS 3405, Faculty of Medicine of Grenoble, University J. Fourier, 38 700 La Tronche, France e-mail: [email protected] H. Hazgui e-mail: [email protected] O. Cohen e-mail: [email protected] J. Demongeot Escuela de Ingenierı´a Civil Informa´tica y Departamento de Ingenierı´a Biomedica, Universitad de Valparaiso, Valparaiso, Chile S. Bandiera A. Henrion-Caude INSERM U 781, Hoˆpital Necker, Universite´ Paris Descartes, 149 rue de Se`vres, 75015 Paris, France e-mail: [email protected] A. Henrion-Caude e-mail: [email protected]
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by the p53 network over the apoptosis/proliferation system and the homeostasis of the energy metabolism. In this last case, we show the role of two kinds of microRNAs, both involved in the control of the mitochondrial genome: (1) nuclear microRNAs, called mitoMirs, inhibiting mitochondrial genes and (2) putative mitochondrial microRNAs inhibiting the tRNAs functioning. Keywords MicroRNAs Chromatin clock control Genetic networks Energetic regulation Mitochondrial respiration Attractors
1 Introduction The microRNAS (often denoted miRs) play an important role of non-specific inhibition in many circumstances of the cell life, like chromatin clock control and have a big influence on many metabolic controls of functions like energy systems, cell cycle and defence systems against pathogens. We present successively in Sects. 2 and 3 their action in controlling chromatin clock and ‘‘immunetworks’’, which are genetic regulatory networks devoted to the control and maintenance of the immunologic system, like the innate system of defence represented by the Toll Like Receptors (TLR), control network already prese
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