Post‐transcriptional regulatory networks play a key role in noise reduction that is conserved from micro‐organisms to mammals

RNA‐binding proteins (RBPs) are core regulators of mRNA transcript stability and translation in prokaryotes and eukaryotes alike. Genome‐wide studies in yeast have shown intriguing relationships between the expression dynamics of RBPs, the structure of post‐transcriptional regulatory networks of RBP–mRNA binding interactions and noise reduction in post‐transcriptionally regulated expression profiles. In the present study, we assembled and compared the genomic properties of RBPs and integrated transcriptional and post‐transcriptional regulatory networks in four species: Escherichia coli, yeast, mouse and human. We found that RBPs are consistently regulated to have minimal levels of protein noise, that known noise‐buffering network motifs are enriched in the integrated networks and that post‐transcriptional feedback loops act as regulators of other regulators. These results support a general model where RBPs are the key regulators of stochastic noise‐buffering in numerous downstream cellular processes. The currently available datasets do not allow clarification of whether post‐transcriptional regulation by RBPs and by noncoding RNAs plays a similar or distinct role, although we found evidence that specific combinations of transcription factors, RBPs and micro‐RNAs jointly regulate known disease pathways in humans, suggesting complementarity rather than redundancy between both modes of post‐transcriptional regulation.