MicroRNAs and Robustness in Biological Regulatory Networks. A Generic Approach with Applications at Different Levels: Physiologic, Metabolic, and Genetic - Systems Biology of Metabolic and Signaling Networks - page 59

Chapter 4
MicroRNAs and Robustness in Biological
Regulatory Networks. A Generic Approach
with Applications at Different Levels:
Physiologic, Metabolic, and Genetic

Jacques Demongeot, Olivier Cohen, and Alexandra Henrion-Caude

Abstract MicroRNAs have been discovered in the noncoding nuclear genome.
They inhibit partly in a nonspecific manner the transcription of numerous genes,
and the corresponding “inhibitory noise” prevents the weakest positive interactions
of the genetic regulatory networks to be actually efficient, hence microRNAs
control the number of attractors of these networks, e.g., by frequently forcing
them to have only one or two possible behaviors for fulfilling a precise cell function
(if we identify a network attractor with a precise differentiated cell state). More
specifically, microRNAs have a great influence on the chromatin clock, which
ensures the controlled mode of updating genetic regulatory networks. We analyze
this influence as well as their impact on important functions like controlling the cell
cycle, improving the defenses of a host against pathogens like viruses, and
maintaining the homeostasis of energy metabolism. In the last case, we show the
role of two types of microRNAs, both involved in the control of the mitochondrial
genome: (1) nuclear microRNAs, called mitoMirs, inhibiting mitochondrial genes
and (2) putative mitochondrial microRNAs located in the noncoding part of the
mitochondrial genome that

inhibit tRNAs function. We show the complex

J. Demongeot
AGIM FRE CNRS-UJF 3405, Faculty of Medicine, University J. Fourier of Grenoble,
38700 La Tronche, France
Escuela de Ingenier ´ a Civil Inform ´ tica y Departamento de Ingenier ´ a Biomedica,
Universidad de Valparaiso, Valparaiso, Chile
e-mail: [e-mail]
O. Cohen ( * )
AGIM FRE CNRS-UJF 3405, Faculty of Medicine, University J. Fourier of Grenoble,
38700 La Tronche, France
e-mail: [e-mail]
A. Henrion-Caude
INSERM U 781, Universit´ Paris Descartes, Hˆpital Necker—Enfants Malades,
149 rue de S`vres, 75015 Paris, France
e-mail: [e-mail]