title: The Ccr4-Not complex interacts with the mRNA export machinery.
abstract: BACKGROUND
  The Ccr4-Not complex is a key eukaryotic regulator of gene transcription and cytoplasmic mRNA degradation. Whether this complex also affects aspects of post-transcriptional gene regulation, such as mRNA export, remains largely unexplored. Human Caf1 (hCaf1), a Ccr4-Not complex member, interacts with and regulates the arginine methyltransferase PRMT1, whose targets include RNA binding proteins involved in mRNA export. However, the functional significance of this regulation is poorly understood.
  
  
  RESULTS
  Here we demonstrate using co-immunoprecipitation approaches that Ccr4-Not subunits interact with Hmt1, the budding yeast ortholog of PRMT1. Furthermore, using genetic and biochemical approaches, we demonstrate that Ccr4-Not physically and functionally interacts with the heterogenous nuclear ribonucleoproteins (hnRNPs) Nab2 and Hrp1, and that the physical association depends on Hmt1 methyltransferase activity. Using mass spectrometry, co-immunoprecipitation and genetic approaches, we also uncover physical and functional interactions between Ccr4-Not subunits and components of the nuclear pore complex (NPC) and we provide evidence that these interactions impact mRNA export.
  
  
  CONCLUSIONS
  Taken together, our findings suggest that Ccr4-Not has previously unrealized functional connections to the mRNA processing/export pathway that are likely important for its role in gene expression. These results shed further insight into the biological functions of Ccr4-Not and suggest that this complex is involved in all aspects of mRNA biogenesis, from the regulation of transcription to mRNA export and turnover.
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Shana C
authors.initials: SC
authors.lastname: Kerr
authors.forename: Nowel
authors.initials: N
authors.lastname: Azzouz
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Fuchs
authors.forename: Martine A
authors.initials: MA
authors.lastname: Collart
authors.forename: Brian D
authors.initials: BD
authors.lastname: Strahl
authors.forename: Anita H
authors.initials: AH
authors.lastname: Corbett
authors.forename: R Nicholas
authors.initials: RN
authors.lastname: Laribee
mesh_terms: D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D022022:Nuclear Pore / Q000378:metabolism; D011061:Poly A / Q000378:metabolism; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D034443:RNA Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012260:Ribonucleases / Q000302:isolation & purification / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; D046912:Multiprotein Complexes; D050505:Mutant Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D011061:Poly A; C475182:HMT1 protein, S cerevisiae; D011484:Protein-Arginine N-Methyltransferases; C078657:CCR4 protein, S cerevisiae; D012260:Ribonucleases