,Gene regulatory network stabilized by pervasive weak repressions: microRNA functions revealed by th

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Food web and gene regulatory networks (GRNs) are large biological networks,both of which can be analyzed using the May-Wigner theory.According to the theory,networks as large as mammalian GRNs would require dedicated gene products for stabilization.We propose that microRNAs (miRNAs) are those products.More than 30% of genes are repressed by miRNAs,but most repressions are too weak to have a phenotypic consequence.The theory shows that (i) weak repressions cumulatively enhance the stability of GRNs,and (ii) broad and weak repressions confer greater stability than a few strong ones.Hence,the diffuse actions ofmiRNAs in mammalian cells appear to function mainly in stabilizing GRNs.The postulated link between mRNA repression and GRN stability can be seen in a different light in yeast,which do not have miRNAs.Yeast cells rely on non-specific RNA nucleases to strongly degrade mRNAs for GRN stability.The strategy is suited to GRNs of small and rapidly dividing yeast cells,but not the larger mammalian cells.In conclusion,the May-Wigner theory,supplanting the analysis of small motifs,provides a mathematical solution to GRN stability,thus linking miRNAs explicitly to ‘developmental canalization’.
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