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

Anagha Joshi, Yvonne Beck, Tom Michoel

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)3501-3512
Number of pages12
JournalFebs Journal
Volume279
Issue number18
DOIs
Publication statusPublished - 2012
EventICSB2012 - 12th International Conference on Systems Biology - Mannheim, Germany
Duration: 28 Aug 20111 Sep 2011

Keywords

  • network comparison
  • post-transcriptional regulation
  • RNA-binding proteins

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