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Elsevier, Journal of Molecular Biology, 3(409), p. 466-479, 2011

DOI: 10.1016/j.jmb.2011.03.064

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Interplay between Posttranscriptional and Posttranslational Interactions of RNA-Binding Proteins

Journal article published in 2011 by Nitish Mittal, Tanja Scherrer, André P. Gerber, Sarath Chandra Janga ORCID
This paper is available in a repository.
This paper is available in a repository.

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Abstract

RNA-binding proteins (RBPs) play important roles in the posttranscriptional control of gene expression. However, our understanding of how RBPs interact with each other at different regulatory levels to coordinate the RNA metabolism of the cell is rather limited. Here, we construct the posttranscriptional regulatory network among 69 experimentally studied RBPs in yeast to show that more than one-third of the RBPs autoregulate their expression at the posttranscriptional level and demonstrate that autoregulatory RBPs show reduced protein noise with a tendency to encode for hubs in this network. We note that in- and outdegrees in the posttranscriptional RBP-RBP regulatory network exhibit gaussian and scale-free distributions, respectively. This network was also densely interconnected with extensive cross-talk between RBPs belonging to different posttranscriptional steps, regulating varying numbers of cellular RNA targets. We show that feed-forward loops and superposed feed-forward/feedback loops are the most significant three-node subgraphs in this network. Analysis of the corresponding protein-protein interaction (posttranslational) network revealed that it is more modular than the posttranscriptional regulatory network. There is significant overlap between the regulatory and protein-protein interaction networks, with RBPs that potentially control each other at the posttranscriptional level tending to physically interact and being part of the same ribonucleoprotein (RNP) complex. Our observations put forward a model wherein RBPs could be classified into those that can stably interact with a limited number of protein partners, forming stable RNP complexes, and others that form transient hubs, having the ability to interact with multiple RBPs forming many RNPs in the cell.