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

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• dc.contributor.author Hollmann, Nele Merret
• dc.contributor.author Jagtap, Pravin Kumar Ankush
• dc.contributor.author Masiewicz, Pawel
• dc.contributor.author Guitart, Tanit
• dc.contributor.author Simon, Bernd
• dc.contributor.author Provaznik, Jan
• dc.contributor.author Stein, Frank
• dc.contributor.author Haberkant, Per
• dc.contributor.author Sweetapple, Lara Jayne
• dc.contributor.author Villacorta, Laura
• dc.contributor.author Mooijman, Dylan
• dc.contributor.author Benes, Vladimir
• dc.contributor.author Savitski, Mikhail M.
• dc.contributor.author Gebauer, Fátima
• dc.contributor.author Hennig, Janosch
• dc.date.accessioned 2020-10-19T07:02:16Z
• dc.date.available 2020-10-19T07:02:16Z
• dc.date.issued 2020
• dc.description.abstract 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Hollmann NM, Jagtap PKA, Masiewicz P, Guitart T, Simon B, Provaznik J, Stein F, Haberkant P, Sweetapple LJ, Villacorta L, Mooijman D, Benes V, Savitski MM, Gebauer F, Hennig J. Pseudo-RNA-binding domains mediate RNA structure specificity in upstream of N-Ras. Cell Rep. 2020; 32(3):107930. DOI: 10.1016/j.celrep.2020.107930
• dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2020.107930
• dc.identifier.issn 2211-1247
• dc.identifier.uri http://hdl.handle.net/10230/45504
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Cell Rep. 2020; 32(3):107930
• dc.rights © 2020 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword NMR spectroscopy
• dc.subject.keyword RNA-binding domains
• dc.subject.keyword RNA-binding proteins
• dc.subject.keyword Cold-shock domains
• dc.subject.keyword Integrative structural biology
• dc.subject.keyword Ribonucleoproteins
• dc.subject.keyword Translation regulation
• dc.title Pseudo-RNA-binding domains mediate RNA structure specificity in upstream of N-Ras
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion