Structural and functional organization of RNA regulons in the post-transcriptional regulatory network of yeast

Post-transcriptional control of mRNA transcript processing by RNA binding proteins (RBPs) is an important step in the regulation of gene expression and protein production. The post-transcriptional regulatory network is similar in complexity to the transcriptional regulatory network and is thought to be organized in RNA regulons, coherent sets of functionally related mRNAs combinatorially regulated by common RBPs. We integrated genome-wide transcriptional and translational expression data in yeast with large-scale regulatory networks of transcription factor and RBP binding interactions to analyze the functional organization of post-transcriptional regulation and RNA regulons at a system level. We found that post-transcriptional feedback loops and mixed bifan motifs are overrepresented in the integrated regulatory network and control the coordinated translation of RNA regulons, manifested as clusters of functionally related mRNAs which are strongly coexpressed in the translatome data. These translatome clusters are more functionally coherent than transcriptome clusters and are expressed with higher mRNA and protein levels and less noise. Our results show how the post-transcriptional network is intertwined with the transcriptional network to regulate gene expression in a coordinated way and that the integration of heterogeneous genome-wide datasets allows to relate structure to function in regulatory networks at a system level.

Joshi, A., Van de Peer, Y., Michoel, T. (2011) Structural and functional organization of RNA regulons in the post-transcriptional regulatory network of yeast. Nucleic Acids Res. 39(21):9108-17.









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