  MicroRNAs (miRNAs) are endogenous 22-nucleotide RNAs, which suppress gene
expression by selectively binding to the 3-noncoding region of specific message
RNAs through base-pairing. Given the diversity and abundance of miRNA targets,
miRNAs appear to functionally interact with various components of many cellular
networks. By analyzing the interactions between miRNAs and a human cellular
signaling network, we found that miRNAs predominantly target positive
regulatory motifs, highly connected scaffolds and most downstream network
components such as signaling transcription factors, but less frequently target
negative regulatory motifs, common components of basic cellular machines and
most upstream network components such as ligands. In addition, when an adaptor
has potential to recruit more downstream components, these components are more
frequently targeted by miRNAs. This work uncovers the principles of miRNA
regulation of signal transduction networks and implies a potential function of
miRNAs for facilitating robust transitions of cellular response to
extracellular signals and maintaining cellular homeostasis.
