Abstract
In the past few decades, gene regulatory networks and cellular signaling networks have been regarded as the major regulatory systems in a cell. In contrast, RNAs have been thought as molecules which are only transferring genetic information for protein production. Recently, microRNAs (miRNAs) have emerged as another layer of gene regulation. They regulate many key biological processes, including cell growth, death, development and differentiation. This discovery hints that cells have more complicated regulation systems. Genes are working together by forming cellular networks. It has become an emerging concept that miRNAs could intertwine with cellular networks to exert their function. Thus, it is essential to understand how miRNAs take part in cellular processes at a systems-level. In this chapter, I will summarize the most recent progress in understanding of miRNA biology at a systems-level: the principles of miRNA regulation of the major cellular networks including signaling, metabolic, protein interaction and gene regulatory networks. A common miRNA regulatory principle is emerging: miRNAs preferentially regulated the genes that have high regulation complexity. In addition, miRNAs preferentially regulate positive regulatory loops, highly connected scaffolds and the most network downstream components of cellular signaling networks, while miRNAs selectively regulate the genes which have specific network structural features on metabolic networks.
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