at Google ScholarTitle data
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:
Pseudo-RNA-Binding Domains Mediate RNA Structure Specificity in Upstream of N-Ras.
In: Cell Reports.
Vol. 32
(2020)
Issue 3
.
- 107930.
ISSN 2211-1247
DOI: https://doi.org/10.1016/j.celrep.2020.107930
Abstract in another language
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.