title: The mRNA export in Caenorhabditis elegans is mediated by Ce-NXF-1, an ortholog of human TAP/NXF and Saccharomyces cerevisiae Mex67p.
abstract: Human TAP and Saccharomyces cerevisiae Mex67p belong to a family of proteins that mediate mRNA export. Computer searches identified previously two Caenorhabditis elegans genes, C15H11.3 and C115H11.6, that encode putative homologs of hTAP and Mex67p (Segref et al., EMBO J, 1997, 16:3256-3271). Using RNA interference experiments in C. elegans, we found that functional knockout of C15H11.3 resulted in nuclear accumulation of poly(A)-containing RNAs and was lethal for both embryos and adult nematodes. No embryonic or progeny abnormality was observed in functional knockout of C15H11.6. Taken together, these data established that the C15H11.3 gene product is an ortholog of hTAP and Mex67p; thus, it was named Ce-NXF-1. Ce-NXF-1 binds RNA directly and is a nucleocytoplasmic shuttle protein accumulating in the nucleoplasm and at the nuclear rim. The rim association is mediated via unique signals present in the C-terminal portion of all TAP/NXF and Mex67p proteins. This region was shown to interact with the FG-repeat domains of nucleoporins Nup98, Nup153, and Nup214, indicating that the rim association occurs through components of the nuclear pore complex. In summary, Ce-NXF-1 belongs together with hTAP and Mex67p to a family of proteins that participate in mRNA export and can provide a direct molecular link between mRNAs and components of the nuclear pore complex. Therefore, despite differences in mRNA metabolism between these species, they utilize a conserved mRNA transport mechanism.
authors.affiliation: Basic Research Laboratory, Human Retrovirus Pathogenesis Section, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
authors.forename: W
authors.initials: W
authors.lastname: Tan
authors.forename: A S
authors.initials: AS
authors.lastname: Zolotukhin
authors.forename: J
authors.initials: J
authors.lastname: Bear
authors.forename: D J
authors.initials: DJ
authors.lastname: Patenaude
authors.forename: B K
authors.initials: BK
authors.lastname: Felber
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D019084:Fluorescent Antibody Technique, Indirect; D018390:Gene Targeting; D005804:Genes, Lethal; D006367:HeLa Cells; D015801:Helminth Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D029543:Nucleocytoplasmic Transport Proteins; D021382:Protein Sorting Signals / Q000502:physiology; D018510:RNA, Helminth / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D020798:Two-Hybrid System Techniques
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; C106898:MEX67 protein, S cerevisiae; D008565:Membrane Proteins; C079377:NUP153 protein, human; C085914:NUP214 protein, human; C418480:NXF-1 protein, C elegans; C122111:NXF1 protein, human; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D021382:Protein Sorting Signals; D018510:RNA, Helminth; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C073119:TAP1 protein, human; C093350:nuclear pore complex protein 98