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Insights into RNA biology from an atlas of mammalian mRNA-binding proteins |
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| Authors: | Castello Alfredo Fischer Bernd Eichelbaum Katrin Horos Rastislav Beckmann Benedikt M Strein Claudia Davey Norman E Humphreys David T Preiss Thomas Steinmetz Lars M Krijgsveld Jeroen Hentze Matthias W |
| Institution: | 1 European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, Heidelberg 69117, Germany 2 Molecular Genetics Division, Victor Chang Cardiac Research Institute, Sydney NSW 2010, Australia 3 Genome Biology Department, The John Curtin School of Medical Research, The Australian National University, Building 131, Garran Road, Acton ACT 0200, Australia |
| Abstract: | RNA-binding proteins (RBPs) determine RNA fate from synthesis to decay. Employing two complementary protocols for covalent UV crosslinking of RBPs to RNA, we describe a systematic, unbiased, and comprehensive approach, termed "interactome capture," to define the mRNA interactome of proliferating human HeLa cells. We identify 860 proteins that qualify as RBPs by biochemical and statistical criteria, adding more than 300 RBPs to those previously known and shedding light on RBPs in disease, RNA-binding enzymes of intermediary metabolism, RNA-binding kinases, and RNA-binding architectures. Unexpectedly, we find that many proteins of the HeLa mRNA interactome are highly intrinsically disordered and enriched in short repetitive amino acid motifs. Interactome capture is broadly applicable to study mRNA interactome composition and dynamics in varied biological settings. |
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