title: The human RBPome: from genes and proteins to human disease.
abstract: RNA binding proteins (RBPs) play a central role in mediating post transcriptional regulation of genes. However less is understood about them and their regulatory mechanisms. In this study, we construct a catalogue of 1344 experimentally confirmed RBPs. The domain architecture of RBPs enabled us to classify them into three groups - Classical (29%), Non-classical (19%) and unclassified (52%). A higher percentage of proteins with unclassified domains reveals the presence of various uncharacterised motifs that can potentially bind RNA. RBPs were found to be highly disordered compared to Non-RBPs (p<2.2e-16, Fisher's exact test), suggestive of a dynamic regulatory role of RBPs in cellular signalling and homeostasis. Evolutionary analysis in 62 different species showed that RBPs are highly conserved compared to Non-RBPs (p<2.2e-16, Wilcox-test), reflecting the conservation of various biological processes like mRNA splicing and ribosome biogenesis. The expression patterns of RBPs from human proteome map revealed that ~40% of them are ubiquitously expressed and ~60% are tissue-specific. RBPs were also seen to be highly associated with several neurological disorders, cancer and inflammatory diseases. Anatomical contexts like B cells, T-cells, foetal liver and foetal brain were found to be strongly enriched for RBPs, implying a prominent role of RBPs in immune responses and different developmental stages. The catalogue and meta-analysis presented here should form a foundation for furthering our understanding of RBPs and the cellular networks they control, in years to come. This article is part of a Special Issue entitled: Proteomics in India.
authors.affiliation: Department of Biohealth Informatics School of Informatics and Computing, Indiana University Purdue University, 719 Indiana Ave Ste 319, Walker Plaza Building, Indianapolis, IN 46202, United States.
authors.forename: Yaseswini
authors.initials: Y
authors.lastname: Neelamraju
authors.affiliation: Department of Biohealth Informatics School of Informatics and Computing, Indiana University Purdue University, 719 Indiana Ave Ste 319, Walker Plaza Building, Indianapolis, IN 46202, United States.
authors.forename: Seyedsasan
authors.initials: S
authors.lastname: Hashemikhabir
authors.affiliation: Department of Biohealth Informatics School of Informatics and Computing, Indiana University Purdue University, 719 Indiana Ave Ste 319, Walker Plaza Building, Indianapolis, IN 46202, United States; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, 5021 Health Information and Translational Sciences (HITS), 410 West 10th Street, Indianapolis, IN 46202, United States; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Medical Research and Library Building, 975 West Walnut Street, Indianapolis, IN 46202, United States. Electronic address: scjanga@iupui.edu.
authors.forename: Sarath Chandra
authors.initials: SC
authors.lastname: Janga
mesh_terms: D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D009422:Nervous System Diseases / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000145:classification / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D020543:Proteome; D016601:RNA-Binding Proteins
keywords: Post-transcriptional regulation; RNA metabolism; RNA-binding; Regulatory networks; Systems biology