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

Structure
Christoph BrockmannMurray Stewart

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.

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Citations

Sep 28, 2013·Nucleic Acids Research·Sonja I KuhlmannMurray Stewart
Oct 2, 2013·Molecular and Cellular Biology·Valérie Grenier St-SauveurFrançois Bachand
Feb 6, 2016·Advances in Anatomic Pathology·Can Ege Yalcin, Tarik Tihan
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Jun 27, 2020·ACS Chemical Neuroscience·Jeremy D BakerBrian C Kraemer
Aug 14, 2021·Genes & Development·Matti TurtolaTorben Heick Jensen
Jul 30, 2015·Genes & Development·L Maximilian ReuterKatja Sträßer

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Methods Mentioned

BETA
chemical shift
NMR
Protein Purification
gel filtration
electrophoresis

Software Mentioned

NIH
CYANA
Sparky
AMBER
XPLOR
CLUSTERPOSE

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