Comprehensive Identification of RNA-Binding Domains in Human Cells

By Alfredo Castello, Bernd Fischer, C. Frese, R. Horos, Anne-Marie Alleaume, Sophia Foehr, Tomaž Curk, Jeroen Krijgsveld, Matthias W. Hentze. Molecules and Cells, 2016

606 citations recorded by the source corpus.

Summary 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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/5b63b6ae01b15b3c37a45d1cf220568e3bd437ea

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In Molecular Biology

1. R. Parker
2. David S. W. Protter
3. M. Rosen
4. Yuan Lin
5. M. Fabian
6. Quaid D. Morris
7. Gene W. Yeo
8. S. Angers

Citations in the corpus

• How RNA binding proteins interact with RNA: molecules and mechanisms (2020, background): “CSDs use Trp more frequently than other domains (p = 2.38 3 10-5).”
• High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. (2018, background): “UBAP2L contains a ubiquitin-associated domain (UBA), three regions predicted to bind to mRNA (aa 239–257, 282–290, and 850–864; Castello et al., 2016), and a domain of unknown function (DUF) region (Figure 7D).”
• RNA-Binding Proteins in Cancer: Old Players and New Actors. (2017, background): “Various mechanisms of RBP regulation have been identified in cancer cells, including genomic alterations, transcriptional and post-transcriptional control, and posttranslational modifications (PTMs).”
• Intrinsically disordered regions contribute promiscuous interactions to RNP granule assembly (2017, background): “Second, IDRs could have promiscuous interactions with RNAs, which is suggested by observations that some IDRs cross-link to RNA in vivo (Castello et al., 2016) and some IDRs bind RNA in vitro (Lin et al., 2015; Molliex et al., 2015).”