Cooperation and competition by RNA-binding proteins in cancer

Abstract

Post-transcriptional regulation of gene expression plays a major role in determining the cellular proteome in health and disease. Post-transcriptional control mechanisms are disrupted in many cancers, contributing to multiple processes of tumorigenesis. RNA-binding proteins (RBPs), the main post-transcriptional regulators, often show altered expression and activity in cancer cells. Dysregulation of RBPs contributes to many cancer phenotypes, functioning in complex regulatory networks with other cellular players such as non-coding RNAs, signaling mediators and transcription factors to alter the expression of oncogenes and tumor suppressor genes. RBPs often function combinatorially, based on their binding to target sequences/structures on shared mRNA targets, to regulate the expression of cancer-related genes. This gives rise to cooperativity and competition between RBPs in mRNA binding and resultant functional outcomes in post-transcriptional processes such as mRNA splicing, stability, export and translation. Cooperation and competition is also observed in the case of interaction of RBPs and microRNAs with mRNA targets. RNA structural change is a common mechanism mediating the cooperative/competitive interplay between RBPs and between RBPs and microRNAs. RNA modifications, leading to changes in RNA structure, add a new dimension to cooperative/competitive binding of RBPs to mRNAs, further expanding the RBP regulatory landscape. Therefore, cooperative/competitive interplay between RBPs is a major determinant of the RBP interactome and post-transcriptional regulation of gene expression in cancer cells.

Keywords: Cancer; Cooperation/competition; MicroRNAs; RNA modifications; RNA structural change; RNA-binding proteins.