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Structural and functional implications of the QUA2 domain on RNA recognition by GLD-1

Daubner, Gerrit M. ; Brümmer, Anneke ; Tocchini, Cristina ; Gerhardy, Stefan ; Ciosk, Rafal ; Zavolan, Mihaela ; Allain, Frédéric H.-T

In: Nucleic Acids Research, 2014, vol. 42, no. 12, p. 8092-8105

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    Titre
    • Structural and functional implications of the QUA2 domain on RNA recognition by GLD-1
    Auteur
    • Daubner, Gerrit M.. Institute of Molecular Biology and Biophysics, Eidgenössische Technische Hochschule (ETH) Zürich, 8093 Zürich, Switzerland
    • Brümmer, Anneke. Biozentrum, University of Basel, 4056 Basel, Switzerland
    • Tocchini, Cristina. Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland
    • Gerhardy, Stefan. Institute of Molecular Biology and Biophysics, Eidgenössische Technische Hochschule (ETH) Zürich, 8093 Zürich, Switzerland
    • Ciosk, Rafal. Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland
    • Zavolan, Mihaela. Biozentrum, University of Basel, 4056 Basel, Switzerland
    • Allain, Frédéric H.-T. Institute of Molecular Biology and Biophysics, Eidgenössische Technische Hochschule (ETH) Zürich, 8093 Zürich, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Nucleic Acids Research, 2014, vol. 42, no. 12, p. 8092-8105. Oxford University Press
    Autre version électronique
    Classification
    • Santé
    Identifiant OAI-PMH
    • oai:doc.rero.ch:299747
    Summary
    The STAR family comprises ribonucleic acid (RNA)-binding proteins that play key roles in RNA-regulatory processes. RNA recognition is achieved by a KH domain with an additional α-helix (QUA2) that seems to extend the RNA-binding surface to six nucleotides for SF1 (Homo sapiens) and seven nucleotides for GLD-1 (Caenorhabditis elegans). To understand the structural basis of this probable difference in specificity, we determined the solution structure of GLD-1 KH-QUA2 with the complete consensus sequence identified in the tra-2 gene. Compared to SF1, the GLD-1 KH-QUA2 interface adopts a different conformation resulting indeed in an additional sequence-specific binding pocket for a uracil at the 5′end. The functional relevance of this binding pocket is emphasized by our bioinformatics analysis showing that GLD-1 binding sites with this 5′end uracil are more predictive for the functional response of the messenger RNAs to gld-1 knockout. We further reveal the importance of the KH-QUA2 interface in vitro and that its alteration in vivo affects the level of translational repression dependent on the sequence of the GLD-1 binding motif. In conclusion, we demonstrate that the QUA2 domain distinguishes GLD-1 from other members of the STAR family and contributes more generally to the modulation of RNA-binding affinity and specificity of KH domain containing proteins