Structural Basis for Polyadenosine-RNA Binding by Nab2 Zn Fingers and Its Function in mRNA Nuclear Export

• Type of Material: Article
• Authors: Christoph Brockmann, Medical Research Council Laboratory of Molecular Biology; Sharon Soucek, Emory University; Sonja I. Kuhlmann, Medical Research Council Laboratory of Molecular Biology; Katherine Mills-Lujan, Emory University; Seth Kelly, Emory University; Ji-Chun Yang, Medical Research Council Laboratory of Molecular Biology; Nahid Iglesias, Department of Cell Biology; Francoise Stutz, Department of Cell Biology; Anita Corbett, Emory University; David Neuhaus, Medical Research Council Laboratory of Molecular Biology; Murray Stewart, Medical Research Council Laboratory of Molecular Biology
• Language: English
• Date: 2012-06-06
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Elsevier Ltd All rights reserved.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.str.2012.03.011
• Title of Journal or Parent Work: Structure
• ISSN: 0969-2126
• Volume: 20
• Issue: 6
• Start Page: 1007
• End Page: 1018
• Grant/Funding Information: Supported in part by a FEBS Fellowship (to C.B.), MRC Grants U105178939 (to M.S.) and U105178934 (to D.N.), and grants from the Wellcome Trust (to M.S.) and NIH (to A.H.C.).
• Keywords: Cell Biology; MRNP DYNAMICS; DOMAIN; BIOPHYSICS; NMR; SACCHAROMYCES-CEREVISIAE; YEAST; TRANSPORT; Life Sciences & Biomedicine; RECOGNITION; GLE1; CELL BIOLOGY; Biophysics; TAIL LENGTH CONTROL; BOX PROTEIN DBP5; BIOCHEMISTRY & MOLECULAR BIOLOGY; Biochemistry & Molecular Biology; Science & Technology
• Research Categories: Chemistry, Biochemistry; Biology, Cell

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.