Roquin binding to target mRNAs involves a winged helix-turn-helix motif

Anja Schuetz; Yasuhiro Murakawa; Eva Rosenbaum; Markus Landthaler; Udo Heinemann

doi:10.1038/ncomms6701

Roquin binding to target mRNAs involves a winged helix-turn-helix motif

Nat Commun. 2014 Dec 11:5:5701. doi: 10.1038/ncomms6701.

Authors

Anja Schuetz¹, Yasuhiro Murakawa², Eva Rosenbaum³, Markus Landthaler², Udo Heinemann⁴

Affiliations

¹ Helmholtz Protein Sample Production Facility, Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany.
² Laboratory for RNA Biology and Posttranscriptional Regulation, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany.
³ Structure and Membrane Interaction of G-Proteins, Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany.
⁴ 1] Helmholtz Protein Sample Production Facility, Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany [2] Chemistry and Biochemistry Institute, Freie Universität Berlin, 14195 Berlin, Germany.

PMID: 25504471
DOI: 10.1038/ncomms6701

Abstract

Roquin proteins mediate mRNA deadenylation by recognizing a conserved class of stem-loop RNA degradation motifs via their Roquin domain. Here we present the crystal structure of a Roquin domain, revealing a mostly helical protein fold bearing a winged helix-turn-helix motif. By combining structural, biochemical and mutation analyses, we gain insight into the mode of RNA binding. We show that the winged helix-turn-helix motif is involved in the binding of constitutive decay elements-containing stem-loop mRNAs. Moreover, we provide biochemical evidence that Roquin proteins are additionally able to bind to duplex RNA and have the potential to be functional in different oligomeric states.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Crystallography, X-Ray
Escherichia coli / genetics
Escherichia coli / metabolism
Gene Expression
Humans
Hydrolysis
Models, Molecular
Nucleic Acid Conformation
Poly A / chemistry*
Protein Binding
Protein Structure, Secondary
Protein Structure, Tertiary
RNA, Double-Stranded / chemistry*
RNA, Messenger / chemistry*
RNA-Binding Proteins / chemistry*
RNA-Binding Proteins / genetics
Recombinant Proteins / chemistry
Recombinant Proteins / genetics
Ubiquitin-Protein Ligases / chemistry*
Ubiquitin-Protein Ligases / genetics

Substances

RC3H1 protein, human
RNA, Double-Stranded
RNA, Messenger
RNA-Binding Proteins
Recombinant Proteins
Poly A
Ubiquitin-Protein Ligases

Associated data

PDB/4ULW