The human RBPome: From genes and proteins to human disease

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• 作者：Yaseswini Neelamraju^a ; Seyedsasan Hashemikhabir^a ; Sarath Chandra Janga^a ; ^b ; ^c ; ^{scjanga@iupui.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Post-transcriptional regulation ; RNA metabolism ; RNA-binding ; Regulatory networks ; Systems biology
• 刊名：Journal of Proteomics
• 出版年：2015
• 出版时间：8 September 2015
• 年：2015
• 卷：127
• 期：part_PA
• 页码：61-70
• 全文大小：2432 K

文摘

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.