Comprehensive identification of RNA-binding domains in human cells

Castello, A. , Fischer, B., Frese, C. K., Horos, R., Alleaume, A.-M., Foehr, S., Curk, T., Krijgsveld, J. and Hentze, M. W. (2016) Comprehensive identification of RNA-binding domains in human cells. Molecular Cell, 63(4), pp. 696-710. (doi: 10.1016/j.molcel.2016.06.029) (PMID:27453046) (PMCID:PMC5003815)

Abstract

Mammalian cells harbor more than a thousand RNA-binding proteins (RBPs), with half of these employing unknown modes of RNA binding. We developed RBDmap to determine the RNA-binding sites of native RBPs on a proteome-wide scale. We identified 1,174 binding sites within 529 HeLa cell RBPs, discovering numerous RNA-binding domains (RBDs). Catalytic centers or protein-protein interaction domains are in close relationship with RNA-binding sites, invoking possible effector roles of RNA in the control of protein function. Nearly half of the RNA-binding sites map to intrinsically disordered regions, uncovering unstructured domains as prevalent partners in protein-RNA interactions. RNA-binding sites represent hot spots for defined posttranslational modifications such as lysine acetylation and tyrosine phosphorylation, suggesting metabolic and signal-dependent regulation of RBP function. RBDs display a high degree of evolutionary conservation and incidence of Mendelian mutations, suggestive of important functional roles. RBDmap thus yields profound insights into native protein-RNA interactions in living cells.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Castello, Professor Alfredo
• Authors: Castello, A., Fischer, B., Frese, C. K., Horos, R., Alleaume, A.-M., Foehr, S., Curk, T., Krijgsveld, J., and Hentze, M. W.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Molecular Cell
• Publisher: Elsevier (Cell Press)
• ISSN: 1097-2765
• ISSN (Online): 1097-4164
• Published Online: 21 July 2016
• Copyright Holders: Copyright © 2016 The Authors
• First Published: First published in Molecular ell 63(4): 696-710
• Publisher Policy: Reproduced under a Creative Commons License