title: Exportin-5, a novel karyopherin, mediates nuclear export of double-stranded RNA binding proteins.
abstract: We have identified a novel human karyopherin (Kap) beta family member that is related to human Crm1 and the Saccharomyces cerevisiae protein, Msn5p/Kap142p. Like other known transport receptors, this Kap binds specifically to RanGTP, interacts with nucleoporins, and shuttles between the nuclear and cytoplasmic compartments. We report that interleukin enhancer binding factor (ILF)3, a double-stranded RNA binding protein, associates with this Kap in a RanGTP-dependent manner and that its double-stranded RNA binding domain (dsRBD) is the limiting sequence required for this interaction. Importantly, the Kap interacts with dsRBDs found in several other proteins and binding is blocked by double-stranded RNA. We find that the dsRBD of ILF3 functions as a novel nuclear export sequence (NES) in intact cells, and its ability to serve as an NES is dependent on the expression of the Kap. In digitonin-permeabilized cells, the Kap but not Crm1 stimulated nuclear export of ILF3. Based on the ability of this Kap to mediate the export of dsRNA binding proteins, we named the protein exportin-5. We propose that exportin-5 is not an RNA export factor but instead participates in the regulated translocation of dsRBD proteins to the cytoplasm where they interact with target mRNAs.
authors.affiliation: Center for Cell Signaling, University of Virginia, Charlottesville, VA 22908, USA. amb7c@virginia.edu
authors.forename: Amy M
authors.initials: AM
authors.lastname: Brownawell
authors.forename: Ian G
authors.initials: IG
authors.lastname: Macara
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism*; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D004072:Digitonin / Q000494:pharmacology; D020869:Gene Expression Profiling; D006801:Humans; D028884:Karyopherins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D050779:Nuclear Factor 90 Proteins; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D010802:Phylogeny; D011485:Protein Binding / Q000187:drug effects; D012330:RNA, Double-Stranded / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014157:Transcription Factors / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D020931:ran GTP-Binding Protein / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D028884:Karyopherins; D050778:NFATC Transcription Factors; D050779:Nuclear Factor 90 Proteins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C446511:XPO5 protein, human; D020931:ran GTP-Binding Protein; D004072:Digitonin