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The Evolutionarily-conserved Polyadenosine RNA Binding Protein, Nab2, Cooperates with Splicing Machinery to Regulate the Fate of pre-mRNA

Soucek, Sharon and Zeng, Yi and Bellur, Deepti L. and Bergkessel, Megan and Morris, Kevin J. and Deng, Qiudong and Duong, Duc and Seyfried, Nicholas T. and Guthrie, Christine and Staley, Jonathan P. and Fasken, Milo B. and Corbett, Anita H. (2016) The Evolutionarily-conserved Polyadenosine RNA Binding Protein, Nab2, Cooperates with Splicing Machinery to Regulate the Fate of pre-mRNA. Molecular and Cellular Biology, 36 (21). pp. 2697-2714. ISSN 0270-7306. PMCID PMC5064217. doi:10.1128/MCB.00402-16. https://resolver.caltech.edu/CaltechAUTHORS:20160822-082031590

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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/U2AF^(65). Taking 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1128/MCB.00402-16DOIArticle
http://mcb.asm.org/content/36/21/2697PublisherArticle
http://mcb.asm.org/content/36/21/2697/suppl/DCSupplementalPublisherSupplemental Material
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064217/PubMed CentralArticle
ORCID:
AuthorORCID
Bergkessel, Megan0000-0002-4530-1224
Additional Information:© 2016 American Society for Microbiology. Accepted manuscript posted online 15 August 2016. We are grateful to members of the Corbett laboratory for helpful discussions and comments. We thank Dr. Stewart Shuman (Sloan-Kettering Institute) and Dr. Beate Schwer (Weill Cornell Medical College) for generously providing the Mud2 and Mud2-RRM3 mutant plasmids. We thank Dr. Christopher Scharer (Emory University) for help with generating the splicing array heat maps. This work, including the efforts of Anita H. Corbett, was funded by HHS (NIH) National Institute of General Medical Sciences (NIGMS) (GM058728). This work, including the efforts of Jonathan Staley, was funded by HHS (NIH) National Institute of General Medical Sciences (NIGMS) (GM062264). This work, including the efforts of Christine Guthrie, was funded by HHS (NIH) National Institute of General Medical Sciences (NIGMS) (GM021119).
Funders:
Funding AgencyGrant Number
NIHGM058728
NIHGM062264
NIHGM021119
National Institute of General Medical SciencesUNSPECIFIED
Subject Keywords:polyadenosine RNA binding protein, Nab2, Mud2, Rrp6, splicing, exosome, ZC3H14, polyadenylation, yeast, RNA surveillance
Issue or Number:21
PubMed Central ID:PMC5064217
DOI:10.1128/MCB.00402-16
Record Number:CaltechAUTHORS:20160822-082031590
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160822-082031590
Official Citation:Evolutionarily Conserved Polyadenosine RNA Binding Protein Nab2 Cooperates with Splicing Machinery To Regulate the Fate of Pre-mRNA Sharon Soucek, Yi Zeng, Deepti L. Bellur, Megan Bergkessel, Kevin J. Morris, Qiudong Deng, Duc Duong, Nicholas T. Seyfried, Christine Guthrie, Jonathan P. Staley, Milo B. Fasken, and Anita H. Corbett Mol. Cell. Biol. November 2016 36:21 18 2697-2714; Accepted manuscript posted online 15 August 2016, doi:10.1128/MCB.00402-16
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:69804
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:22 Aug 2016 20:51
Last Modified:11 Nov 2021 04:20

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