Network motifs are enriched with transcription factors whose transcripts have short half-lives.

Network motifs, the recurring regulatory structural patterns in networks, can self-organize to produce networks because of the large ratio of genes to transcription factors (TFs) in genomes. We find a common design principle of these motifs: the TFs whose transcripts have short half-lives are significantly enriched in motifs and hubs. This enrichment becomes one of the driving forces for the emergence of the network scale-free topology, enables the network to adapt quickly to environmental changes and mitigates gene expression fluctuations. Motifs are classified into subtypes that are preferentially used in different cellular conditions.