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.
Highlights
RNA-binding proteins (RBPs) play important roles in cellular homeostasis by controlling gene expression at the post-transcriptional level
To determine the regulatory effect of RBPs at the post-transcriptional level compared to other regulatory factors, such as transcription factors (TFs), microRNAs and long noncoding RNAs, their expression levels were compared for different human tissues
We showed that there is a unique signature of approximately 30 RBPs that had significantly increased expression levels across six out of nine cancers profiled
Summary
RNA-binding proteins (RBPs) play important roles in cellular homeostasis by controlling gene expression at the post-transcriptional level. RBPs form dynamic ribonucleoprotein (RNP) complexes, often in a highly combinatorial fashion that can affect all aspects of the life of RNA [1,2,3] Due to their central role in controlling gene expression at the post-transcriptional level, alterations in expression or mutations in either RBPs or their binding sites in target transcripts have. Another example is the cell-specific alternative splicing of FAS (Fas cell surface death receptor, a member of the TNF receptor superfamily) mRNA This has been linked to cancer predisposition depending on whether the pro- or anti-apoptotic protein form is produced as a result of the interplay between various RBPs on the FAS transcript [11,12,13,14]. Disruption of the functionality of RBPs, without directly acting on oncogenic genes, has been shown to affect alternative splicing regulation or the regulation of alternative cleavage mechanisms on transcripts, which can lead to the development of cancer [15,16]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
