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Pseudo-Rna Binding Domains Mediate Rna Structure Specificity in Upstream of N-Ras

46 Pages Posted: 22 May 2020 Sneak Peek Status: Under Review

See all articles by Nele Merret Hollmann

Nele Merret Hollmann

European Molecular Biology Laboratory (EMBL)- Germany - Structural and Computational Biology Unit; Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences

Pravin Kumar Ankush Jagtap

European Molecular Biology Laboratory (EMBL)- Germany - Structural and Computational Biology Unit

Pawel Masiewicz

European Molecular Biology Laboratory (EMBL)- Germany - Structural and Computational Biology Unit

Tanit Guitart

Barcelona Institute of Science and Technology (BIST) - Gene Regulation, Stem Cells and Cancer Program

Bernd Simon

European Molecular Biology Laboratory (EMBL)- Germany - Structural and Computational Biology Unit

Jan Provaznik

Genomics Core Facility, EMBL Heidelberg

Frank Stein

European Molecular Biology Laboratory (EMBL)- Germany; Proteomics Core Facility, EMBL Heidelberg

Per Haberkant

Proteomics Core Facility, EMBL Heidelberg

Lara Sweetapple

European Molecular Biology Laboratory (EMBL)- Germany - Structural and Computational Biology Unit

Laura Villacorte

Genomics Core Facility, EMBL Heidelberg

Dylan Mooijman

European Molecular Biology Laboratory (EMBL)- Germany - Developmental Biology Unit

Vladimir Benes

Genomics Core Facility, EMBL Heidelberg

Mikhail M. Savitski

Proteomics Core Facility, EMBL Heidelberg; Genome Biology Unit, EMBL Heidelberg

Fátima Gebauer

Barcelona Institute of Science and Technology (BIST) - Gene Regulation, Stem Cells and Cancer Program; Universitat Pompeu Fabra

Janosch Hennig

European Molecular Biology Laboratory (EMBL)- Germany - Structural and Computational Biology Unit

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Abstract

RNA binding proteins (RBPs) commonly feature multiple RNA binding domains (RBDs), which provides these proteins with a modular architecture. Accumulating evidence supports that RBP architectural modularity and adaptability defines 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 now 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 canonical/non-canonical CSD interactions impacted RNA binding, Unr-mediated translation regulation, and the Unr-dependent RNA interactome. Taken together, our studies revealed 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.

Keywords: Unr, RNA binding protein, non-canonical cold-shock domains, RNA binding specificity, translational control, pseudo-RNA binding domains, RNA-protein interactions

Suggested Citation

Hollmann, Nele Merret and Ankush Jagtap, Pravin Kumar and Masiewicz, Pawel and Guitart, Tanit and Simon, Bernd and Provaznik, Jan and Stein, Frank and Haberkant, Per and Sweetapple, Lara and Villacorte, Laura and Mooijman, Dylan and Benes, Vladimir and Savitski, Mikhail M. and Gebauer, Fátima and Hennig, Janosch, Pseudo-Rna Binding Domains Mediate Rna Structure Specificity in Upstream of N-Ras. Available at SSRN: https://ssrn.com/abstract=3595718 or http://dx.doi.org/10.2139/ssrn.3595718
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Nele Merret Hollmann

European Molecular Biology Laboratory (EMBL)- Germany - Structural and Computational Biology Unit ( email )

Heidelberg, 69117
Germany

Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences ( email )

Pravin Kumar Ankush Jagtap

European Molecular Biology Laboratory (EMBL)- Germany - Structural and Computational Biology Unit ( email )

Heidelberg, 69117
Germany

Pawel Masiewicz

European Molecular Biology Laboratory (EMBL)- Germany - Structural and Computational Biology Unit ( email )

Heidelberg, 69117
Germany

Tanit Guitart

Barcelona Institute of Science and Technology (BIST) - Gene Regulation, Stem Cells and Cancer Program ( email )

Dr. Aiguader 88
Barcelona, 08003
Spain

Bernd Simon

European Molecular Biology Laboratory (EMBL)- Germany - Structural and Computational Biology Unit

Heidelberg, 69117
Germany

Jan Provaznik

Genomics Core Facility, EMBL Heidelberg ( email )

Frank Stein

European Molecular Biology Laboratory (EMBL)- Germany

Meyerhofstraße 1
Heidelberg, 69117
Germany

Proteomics Core Facility, EMBL Heidelberg

Per Haberkant

Proteomics Core Facility, EMBL Heidelberg ( email )

Lara Sweetapple

European Molecular Biology Laboratory (EMBL)- Germany - Structural and Computational Biology Unit ( email )

Heidelberg, 69117
Germany

Laura Villacorte

Genomics Core Facility, EMBL Heidelberg ( email )

Dylan Mooijman

European Molecular Biology Laboratory (EMBL)- Germany - Developmental Biology Unit ( email )

Heidelberg, 69117
Germany

Vladimir Benes

Genomics Core Facility, EMBL Heidelberg ( email )

Mikhail M. Savitski

Proteomics Core Facility, EMBL Heidelberg ( email )

Genome Biology Unit, EMBL Heidelberg ( email )

Fátima Gebauer

Barcelona Institute of Science and Technology (BIST) - Gene Regulation, Stem Cells and Cancer Program ( email )

Dr. Aiguader 88
Barcelona, 08003
Spain

Universitat Pompeu Fabra ( email )

Ramon Trias Fargas, 25-27
Barcelona, E-08005
Spain

Janosch Hennig (Contact Author)

European Molecular Biology Laboratory (EMBL)- Germany - Structural and Computational Biology Unit ( email )

Heidelberg, 69117
Germany

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