Roquin recognizes a non-canonical hexaloop structure in the 3′-UTR of Ox40

Robert Janowski, Gitta A. Heinz, Andreas Schlundt, Nina Wommelsdorf, Sven Brenner, Andreas R. Gruber, Michael Blank, Thorsten Buch, Raymund Buhmann, Mihaela Zavolan, Dierk Niessing (), Vigo Heissmeyer () and Michael Sattler ()
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Robert Janowski: Group Intracellular Transport and RNA Biology, Institute of Structural Biology, Helmholtz Zentrum München
Gitta A. Heinz: Research Unit Molecular Immune Regulation, Helmholtz Zentrum München
Andreas Schlundt: Institute of Structural Biology, Helmholtz Zentrum München
Nina Wommelsdorf: Research Unit Molecular Immune Regulation, Helmholtz Zentrum München
Sven Brenner: Research Unit Molecular Immune Regulation, Helmholtz Zentrum München
Andreas R. Gruber: Biozentrum, University of Basel and Swiss Institute of Bioinformatics
Michael Blank: AptaIT GmbH
Thorsten Buch: Institute of Laboratory Animal Science, University of Zurich
Raymund Buhmann: AptaIT GmbH
Mihaela Zavolan: Biozentrum, University of Basel and Swiss Institute of Bioinformatics
Dierk Niessing: Group Intracellular Transport and RNA Biology, Institute of Structural Biology, Helmholtz Zentrum München
Vigo Heissmeyer: Research Unit Molecular Immune Regulation, Helmholtz Zentrum München
Michael Sattler: Institute of Structural Biology, Helmholtz Zentrum München

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract The RNA-binding protein Roquin is required to prevent autoimmunity. Roquin controls T-helper cell activation and differentiation by limiting the induced expression of costimulatory receptors such as tumor necrosis factor receptor superfamily 4 (Tnfrs4 or Ox40). A constitutive decay element (CDE) with a characteristic triloop hairpin was previously shown to be recognized by Roquin. Here we use SELEX assays to identify a novel U-rich hexaloop motif, representing an alternative decay element (ADE). Crystal structures and NMR data show that the Roquin-1 ROQ domain recognizes hexaloops in the SELEX-derived ADE and in an ADE-like variant present in the Ox40 3′-UTR with identical binding modes. In cells, ADE-like and CDE-like motifs cooperate in the repression of Ox40 by Roquin. Our data reveal an unexpected recognition of hexaloop cis elements for the posttranscriptional regulation of target messenger RNAs by Roquin.

Date: 2016
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DOI: 10.1038/ncomms11032

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