title: The Evolutionarily-conserved Polyadenosine RNA Binding Protein, Nab2, Cooperates with Splicing Machinery to Regulate the Fate of pre-mRNA.
abstract: Numerous RNA binding proteins are deposited onto an mRNA transcript to modulate post-transcriptional processing events ensuring proper mRNA maturation. Defining the interplay between RNA binding proteins that couple mRNA biogenesis events is crucial for understanding how gene expression is regulated. To explore how RNA binding proteins control mRNA processing, we investigated a role for the evolutionarily conserved polyadenosine RNA binding protein, Nab2, in mRNA maturation within the nucleus. This work reveals that nab2 mutant cells accumulate intron-containing pre-mRNA in vivo We extend this analysis to identify genetic interactions between mutant alleles of nab2 and genes encoding the splicing factor, MUD2, and the RNA exosome, RRP6, with in vivo consequences of altered pre-mRNA splicing and poly(A) tail length control. As further evidence linking Nab2 proteins to splicing, an unbiased proteomic analysis of vertebrate Nab2, ZC3H14, identifies physical interactions with numerous components of the spliceosome. We validated the interaction between ZC3H14 and U2AF2/U2AF65Taking all the findings into consideration, we present a model where Nab2/ZC3H14 interacts with spliceosome components to allow proper coupling of splicing with subsequent mRNA processing steps contributing to a kinetic proofreading step that allows properly processed mRNA to exit the nucleus and escape Rrp6-dependent degradation.
authors.affiliation: Graduate Program in Biochemistry, Cell, and Developmental Biology, Emory University School of Medicine, Atlanta, GA, USA Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Soucek
authors.affiliation: Graduate Program in Cell and Molecular Biology, The University of Chicago, Chicago, IL, USA Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL, USA.
authors.forename: Deepti L
authors.initials: DL
authors.lastname: Bellur
authors.affiliation: Division of Geological and Planetary Sciences California Institute of Technology, Pasadena, California, USA Department of Biochemistry and Biophysics, University of California, San Francisco, California, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Bergkessel
authors.affiliation: Graduate Program in Biochemistry, Cell, and Developmental Biology, Emory University School of Medicine, Atlanta, GA, USA Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Morris
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Qiudong
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Duc
authors.initials: D
authors.lastname: Duong
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Seyfried
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, California, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Guthrie
authors.affiliation: Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Staley
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA acorbe2@emory.edu mfasken@emory.edu.
authors.forename: Milo B
authors.initials: MB
authors.lastname: Fasken
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA acorbe2@emory.edu mfasken@emory.edu.
authors.forename: Anita H
authors.initials: AH
authors.lastname: Corbett