Gene regulatory network stabilized by pervasive weak repressions: micro RNA functions revealed by the May–Wigner theory  

作　　者：Yuxin Chen Yang Shen Pei Lin Ding Tong Yixin Zhao Stefano Allesina Xu Shen Chung-I Wu 

机构地区：[1]School of Life Science,Sun Yat-Sen University,Guangzhou 510275,China [2]Target Discovery Research,Boehringer Ingelheim Pharma GmbH&Co KG,88397 Biberach an der RiB,Germany [3]Department of Biostatistics,School of Public Health,Yale University,New Haven,CT 06520,USA [4]Department of Ecology and Evolution,University of Chicago,Chicago,IL 60637,USA

出　　处：《National Science Review》2019年第6期1176-1188,共13页国家科学评论（英文版）

基　　金：supported by the National Natural Science Foundation of China(31730046 and 91731301);the National Basic Research Program(973 Program)of China(2014CB542006);the 985 Project(33000–18841204);National Institute of Health,USA(5 R01 GM058686-09 to WU,Chung-I)

摘　　要：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 m ost 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 of miRNAs 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-W igner theory,supplanting the analysis of small motifs,provides a mathematical solution to GRN stability,thus linking miRNAs explicitly to‘developmental canalization’.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 micro RNAs(mi RNAs) are those products. More than 30% of genes are repressed by mi RNAs, 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 of mi RNAs in mammalian cells appear to function mainly in stabilizing GRNs. The postulated link between m RNA repression and GRN stability can be seen in a different light in yeast, which do not have mi RNAs. Yeast cells rely on non-specific RNA nucleases to strongly degrade m RNAs 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 mi RNAs explicitly to ’developmental canalization’.

关 键 词：micro RNAs network stability CANALIZATION May-Wigner theory systems biology RNA crosstalk 

分 类 号：Q811.4[生物学—生物工程]