Exp5 exports eEF1A via tRNA from nuclei and synergizes with other transport pathways to confine translation to the cytoplasm.
Importin beta-type transport receptors mediate the vast majority of transport pathways between cell nucleus and cytoplasm. We identify here the translation elongation factor 1A (eEF1A) as the predominant nuclear export substrate of RanBP21/exportin 5 (Exp5). This cargo-exportin interaction is rather un usual in that eEF1A binds the exportin not directly, but instead via aminoacylated tRNAs. Exp5 thus represents the second directly RNA-binding exportin and mediates tRNA export in parallel with exportin-t. It was suggested recently that 10-15% of the cellular translation would occur in the nucleus. Our data rule out such a scenario and instead suggest that nuclear translation is actively suppressed by the nuclear export machinery. We found that the vast majority of translation initiation factors (eIF2, eIF2B, eIF3, eIF4A1, eIF5 and eIF5B), all three elongation factors (eEF1A, eEF1B and eEF2) and the termination factor eRF1 are strictly excluded from nuclei. Besides Exp5 and importin 13, CRM1 and as yet unidentified exportins also contribute to the depletion of translation factors from nuclei.
Bohnsack
Markus T
MT
ZMBH, INF 282, D-69120 Heidelberg, Germany.
Regener
Kathrin
K
Schwappach
Blanche
B
Saffrich
Rainer
R
Paraskeva
Efrosyni
E
Hartmann
Enno
E
Görlich
Dirk
D
D016475:3T3 Cells; D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D020224:Expressed Sequence Tags; D006160:Guanosine Triphosphate / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000502:physiology*; D046911:Macromolecular Substances; D008647:Mesocricetus; D051379:Mice; D008969:Molecular Sequence Data; D020648:Peptide Elongation Factor 1 / Q000378:metabolism*; D014176:Protein Biosynthesis; D025941:Protein Interaction Mapping; D020033:Protein Isoforms / Q000378:metabolism; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins / Q000502:physiology; D020931:ran GTP-Binding Protein / Q000378:metabolism; D000097606:Exportin 1 Protein
D029721:Drosophila Proteins; D039642:Eukaryotic Initiation Factors; D006160:Guanosine Triphosphate; D028884:Karyopherins; D046911:Macromolecular Substances; D020648:Peptide Elongation Factor 1; D020033:Protein Isoforms; D012346:RNA, Transfer, Amino Acyl; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D020931:ran GTP-Binding Protein; D000097606:Exportin 1 Protein; C514587:RanBP21 protein, Drosophila; C446511:XPO5 protein, human; C499175:Xpo5 protein, mouse