The human RBPome: from genes and proteins to human disease

J Proteomics. 2015 Sep 8;127(Pt A):61-70. doi: 10.1016/j.jprot.2015.04.031. Epub 2015 May 14.

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.

Keywords: Post-transcriptional regulation; RNA metabolism; RNA-binding; Regulatory networks; Systems biology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Neoplasm Proteins* / genetics
  • Neoplasm Proteins* / metabolism
  • Neoplasms* / genetics
  • Neoplasms* / metabolism
  • Nervous System Diseases* / genetics
  • Nervous System Diseases* / metabolism
  • Proteome* / classification
  • Proteome* / genetics
  • Proteome* / metabolism
  • RNA-Binding Proteins* / classification
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism

Substances

  • Neoplasm Proteins
  • Proteome
  • RNA-Binding Proteins