Computational analysis of cooperation and competition mechanisms between RNA-binding proteins

Gene expression is regulated at five different levels, namely epigenetic, transcriptional, post-transcriptional, translational and post-translational. The post-transcriptional regulatory layer accounts for all the events taking place between transcription and translation and involves a myriad of trans and cis factors densely interconnected. Among the regulatory trans-elements forming this network, RNA-binding proteins (RBPs) play key roles in post-transcriptional regulation of gene expression (PTR). Understanding RBPs behavior is therefore crucial given their participation in all stages of the mRNA life cycle. Although an increasing amount of work has highlighted the relevance of RBP-RBP interactions for PTR, only recent studies have focused on the development of comprehensive approaches for prediction of potential RBP-RBP interactions previously unreported. Despite these steps toward a comprehensive RBP-RBP interaction map, the underlying driver mechanisms of such interactions are still not well characterized. The present work aims thus at providing insights into the complexity of this highly interconnected regulatory network. Leveraging positional information of RNA-binding sites from crosslinking and immunoprecipitation assays, we provide an initial approach to discern between RBP cooperation and competition. In addition, we evaluated the impact of multiple features on the RBP-RBP interaction modalities, eventually directing our focus towards the role of post-translational modifications (PTMs) in these mechanisms. Our findings suggest that potential PTM sites influence the modality of RBP-RBP interactions thus being a candidate determinant factor of cooperative and competitive behaviors.