Pseudo-RNA-binding domains mediate RNA structure specificity in upstream of N-Ras

RNA-binding proteins (RBPs) commonly feature multiple RNA-binding domains (RBDs), which provide these proteins with a modular architecture. Accumulating evidence supports that RBP architectural modularity and adaptability define the specificity of their interactions with RNA. However, how multiple R...

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Detalles Bibliográficos
Autores: Hollmann, Nele Merret, Jagtap, Pravin Kumar Ankush, Masiewicz, Pawel, Guitart, Tanit, Simon, Bernd, Provaznik, Jan, Stein, Frank, Haberkant, Per, Sweetapple, Lara Jayne, Villacorta, Laura, Mooijman, Dylan, Benes, Vladimir, Savitski, Mikhail M., Gebauer, Fátima, Hennig, Janosch
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/45504
Acceso en línea:http://hdl.handle.net/10230/45504
http://dx.doi.org/10.1016/j.celrep.2020.107930
Access Level:acceso abierto
Palabra clave:NMR spectroscopy
RNA-binding domains
RNA-binding proteins
Cold-shock domains
Integrative structural biology
Ribonucleoproteins
Translation regulation
Descripción
Sumario:RNA-binding proteins (RBPs) commonly feature multiple RNA-binding domains (RBDs), which provide these proteins with a modular architecture. Accumulating evidence supports that RBP architectural modularity and adaptability define the specificity of their interactions with RNA. However, how multiple RBDs recognize their cognate single-stranded RNA (ssRNA) sequences in concert remains poorly understood. Here, we use Upstream of N-Ras (Unr) as a model system to address this question. Although reported to contain five ssRNA-binding cold-shock domains (CSDs), we demonstrate that Unr includes an additional four CSDs that do not bind RNA (pseudo-RBDs) but are involved in mediating RNA tertiary structure specificity by reducing the conformational heterogeneity of Unr. Disrupting the interactions between canonical and non-canonical CSDs impacts RNA binding, Unr-mediated translation regulation, and the Unr-dependent RNA interactome. Taken together, our studies reveal a new paradigm in protein-RNA recognition, where interactions between RBDs and pseudo-RBDs select RNA tertiary structures, influence RNP assembly, and define target specificity.

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