title: NXF1/p15 heterodimers are essential for mRNA nuclear export in Drosophila.
abstract: The conserved family of NXF proteins has been implicated in the export of messenger RNAs from the nucleus. In metazoans, NXFs heterodimerize with p15. The yeast genome encodes a single NXF protein (Mex67p), but there are multiple nxf genes in metazoans. Whether metazoan NXFs are functionally redundant, or their multiplication reflects an adaptation to a greater substrate complexity or to tissue-specific requirements has not been established. The Drosophila genome encodes one p15 homolog and four putative NXF proteins (NXF1 to NXF4). Here we show that depletion of the endogenous pools of NXF1 or p15 from Drosophila cells inhibits growth and results in a rapid and robust accumulation of polyadenylated RNAs within the nucleus. Fluorescence in situ hybridizations show that export of both heat-shock and non-heat-shock mRNAs, as well as intron-containing and intronless mRNAs is inhibited. Depleting endogenous NXF2 or NXF3 has no apparent phenotype. Moreover, NXF4 is not expressed at detectable levels in cultured Drosophila cells. We conclude that Dm NXF1/p15 heterodimers only (but not NXF2-NXF4) mediate the export of the majority of mRNAs in Drosophila cells and that the other members of the NXF family play more specialized or different roles.
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Herold
authors.forename: T
authors.initials: T
authors.lastname: Klymenko
authors.forename: E
authors.initials: E
authors.lastname: Izaurralde
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism*; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019281:Dimerization; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D029721:Drosophila Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics; D018869:Heat-Shock Response; D019476:Insect Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D029721:Drosophila Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C089272:Hsp83 protein, Drosophila; D019476:Insect Proteins; C122111:NXF1 protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins