title: Post-transcriptional regulatory networks play a key role in noise reduction that is conserved from micro-organisms to mammals.
abstract: 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.
authors.affiliation: Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, UK.
authors.forename: Anagha
authors.initials: A
authors.lastname: Joshi
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Beck
authors.forename: Tom
authors.initials: T
authors.lastname: Michoel
mesh_terms: D000818:Animals; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D049490:Systems Biology; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D029968:Escherichia coli Proteins; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors