Abstract

BackgroundRNA-binding proteins regulate a number of cellular processes, including synthesis, folding, translocation, assembly and clearance of RNAs. Recent studies have reported that an unexpectedly large number of proteins are able to interact with RNA, but the partners of many RNA-binding proteins are still uncharacterized.ResultsWe combined prediction of ribonucleoprotein interactions, based on catRAPID calculations, with analysis of protein and RNA expression profiles from human tissues. We found strong interaction propensities for both positively and negatively correlated expression patterns. Our integration of in silico and ex vivo data unraveled two major types of protein–RNA interactions, with positively correlated patterns related to cell cycle control and negatively correlated patterns related to survival, growth and differentiation. To facilitate the investigation of protein–RNA interactions and expression networks, we developed the catRAPID express web server.ConclusionsOur analysis sheds light on the role of RNA-binding proteins in regulating proliferation and differentiation processes, and we provide a data exploration tool to aid future experimental studies.

Highlights

  • RNA-binding proteins regulate a number of cellular processes, including synthesis, folding, translocation, assembly and clearance of RNAs

  • In this study, we focused on the mRNA interactomes of RNA-binding protein (RBP) detected through nucleotide-enhanced UV cross-linking and oligo(dT) purification approaches [1,2]

  • Interrogating the Gene Expression Omnibus (GEO) [29] and ArrayExpress databases [30], we found two human proteins, ELAV-like protein 1 [31] and Protein lin-28 homolog B (LIN28B) [32,33], whose knock-down has been shown to alter the expression of target genes identified by PAR-CLIP

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Summary

Introduction

RNA-binding proteins regulate a number of cellular processes, including synthesis, folding, translocation, assembly and clearance of RNAs. Approaches based on nucleotide-enhanced UV cross-linking and oligo(dT) purification have shown that a number of proteins are able to bind to RNA [1,2]. We combine our predictions of protein–RNA interactions, based on catRAPID calculations [19,20], with the information obtained from expression data to investigate constitutive regulatory mechanisms. The catRAPID approach has been previously employed to predict protein associations with non-coding RNAs [21,22] as well as ribonucleoprotein interactions linked to neurodegenerative diseases [23,24]. The catRAPID omics algorithm, validated using photoactivatable-ribonucleoside-enhanced cross-linking and immunoprecipitation (PAR-CLIP) data, has been recently developed to predict protein–RNA associations at the transcriptomic and proteomic levels [26]

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