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Structural basis for polyadenosine-RNA binding by Nab2 Zn fingers and its function in mRNA nuclear export

Brockmann, Christoph
Soucek, Sharon
Kuhlmann, Sonja I.
Mills-Lujan, Katherine
Kelly, Seth M.
Yang, Ji-Chun
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Published in Structure. 2012, vol. 20, no. 6, p. 1007-18
Abstract Polyadenylation regulation and efficient nuclear export of mature mRNPs both require the polyadenosine-RNA-binding protein, Nab2, which contains seven CCCH Zn fingers. We describe here the solution structure of fingers 5-7, which are necessary and sufficient for high-affinity polyadenosine-RNA binding, and identify key residues involved. These Zn fingers form a single structural unit. Structural coherence is lost in the RNA-binding compromised Nab2-C437S mutant, which also suppresses the rat8-2 allele of RNA helicase Dbp5. Structure-guided Nab2 variants indicate that dbp5(rat8-2) suppression is more closely linked to hyperadenylation and suppression of mutant alleles of the nuclear RNA export adaptor, Yra1, than to affinity for polyadenosine-RNA. These results indicate that, in addition to modulating polyA tail length, Nab2 has an unanticipated function associated with generating export-competent mRNPs, and that changes within fingers 5-7 lead to suboptimal assembly of mRNP export complexes that are more easily disassembled by Dbp5 upon reaching the cytoplasm.
Keywords Active Transport, Cell NucleusAdenosine/chemistryAmino Acid SequenceAmino Acid SubstitutionConserved SequenceModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedNuclear Magnetic Resonance, BiomolecularNucleocytoplasmic Transport Proteins/chemistry/genetics/metabolismPolymers/chemistryProtein BindingProtein Structure, TertiaryRNA TransportRNA, Messenger/chemistryRNA-Binding Proteins/chemistry/genetics/metabolismSaccharomyces cerevisiae/genetics/growth & developmentSaccharomyces cerevisiae Proteins/chemistry/genetics/metabolismSurface PropertiesThermodynamicsZinc Fingers
PMID: 22560733
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Research group Groupe Stutz
Swiss National Science Foundation: 31003A_130292
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BROCKMANN, Christoph et al. Structural basis for polyadenosine-RNA binding by Nab2 Zn fingers and its function in mRNA nuclear export. In: Structure, 2012, vol. 20, n° 6, p. 1007-18. doi: 10.1016/j.str.2012.03.011 https://archive-ouverte.unige.ch/unige:36375

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Deposited on : 2014-05-06

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