Aromatic side-chain conformational switch on the surface of the RNA Recognition Motif enables RNA discrimination
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Diarra Dit Konté, Nana
Damberger, Fred F.
Allain, Frédéric H.-T.
- Journal Article
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Rights / licenseCreative Commons Attribution 4.0 International
The cyclooxygenase-2 is a pro-inflammatory and cancer marker, whose mRNA stability and translation is regulated by the CUG-binding protein 2 interacting with AU-rich sequences in the 3′ untranslated region. Here, we present the solution NMR structure of CUG-binding protein 2 RRM3 in complex with 5′-UUUAA-3′ originating from the COX-2 3′-UTR. We show that RRM3 uses the same binding surface and protein moieties to interact with AU- and UG-rich RNA motifs, binding with low and high affinity, respectively. Using NMR spectroscopy, isothermal titration calorimetry and molecular dynamics simulations, we demonstrate that distinct sub-states characterized by different aromatic side-chain conformations at the RNA-binding surface allow for high- or low-affinity binding with functional implications. This study highlights a mechanism for RNA discrimination possibly common to multiple RRMs as several prominent members display a similar rearrangement of aromatic residues upon binding their targets Show more
Journal / seriesNature Communications
Pages / Article No.
PublisherNature Publishing Group
Organisational unit03591 - Allain, Frédéric / Allain, Frédéric
170130 - NMR structure determination of protein-RNA complexes involved in pre-mRNA splicing and translation regulation (SNF)
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