Dissecting the expression landscape of RNA-binding proteins in human cancers

Abstract

BackgroundRNA-binding proteins (RBPs) play important roles in cellular homeostasis by controlling gene expression at the post-transcriptional level.ResultsWe explore the expression of more than 800 RBPs in sixteen healthy human tissues and their patterns of dysregulation in cancer genomes from The Cancer Genome Atlas project. We show that genes encoding RBPs are consistently and significantly highly expressed compared with other classes of genes, including those encoding regulatory components such as transcription factors, miRNAs and long non-coding RNAs. We also demonstrate that a set of RBPs, numbering approximately 30, are strongly upregulated (SUR) across at least two-thirds of the nine cancers profiled in this study. Analysis of the protein–protein interaction network properties for the SUR and non-SUR groups of RBPs suggests that path length distributions between SUR RBPs is significantly lower than those observed for non-SUR RBPs. We further find that the mean path lengths between SUR RBPs increases in proportion to their contribution to prognostic impact. We also note that RBPs exhibiting higher variability in the extent of dysregulation across breast cancer patients have a higher number of protein–protein interactions. We propose that fluctuating RBP levels might result in an increase in non-specific protein interactions, potentially leading to changes in the functional consequences of RBP binding. Finally, we show that the expression variation of a gene within a patient group is inversely correlated with prognostic impact.ConclusionsOverall, our results provide a roadmap for understanding the impact of RBPs on cancer pathogenesis.

Identification of RNA-Binding Protein LARP4B as a Tumor Suppressor in Glioma

“…We found that the RNAbinding ability of LARP4B contributed to its growth-inhibitory function, indicating that LARP4B suppresses glioma cell growth through an interaction with RNA. Deregulated expression of RNAbinding proteins is commonly observed in cancer (38), and emerging evidence indicates causative roles for the dysregulation of RNA-binding proteins in cancer progression (39). Alternative splicing of mRNA precursors (pre-mRNA) is one of the mechanisms through which dysregulation of RNA-binding proteins confers growth advantage to cancer cells, because cancer cells favor the production of protein isoforms that promote growth and survival (17,40).…”

The human RBPome: From genes and proteins to human disease

“…One of the pivotal players that are responsible for post-transcriptional regulatory control in eukaryotic organisms are the RNA binding proteins (RBPs). RBPs bind single or double stranded RNA and determine their fate from synthesis to decay [1][2][3][4][5]. They possess one or more domains that can recognize RNA in a sequence specific manner and hence conferring different binding affinities and specificities.…”

“…When bound to an mRNA, these proteins control all the major steps of an mRNA's life, including splicing, export, localization, translation and degradation [1,3,4]. Due to their multi-functionality, RBPs become the most prominent of the post transcriptional machinery and any alteration in their function can cause deleterious effects which could lead to numerous complex disorders [2,7,8]. Hence, it becomes important to understand the structural and functional characteristics of RBPs in humans.…”

Effects of HuR downregulation on anaplastic thyroid cancer cells

“…These mechanisms are altered in several diseases, including cancer, and this could be due to an aberrant expression and activity of RNA-binding proteins (RBPs) (2,3). These proteins are key regulators of post-transcriptional gene expression and among them, one the most known RBP to be implicated in tumorigenesis is Hu antigen R (HuR) (4)(5)(6).…”