title: The principal mRNA nuclear export factor NXF1:NXT1 forms a symmetric binding platform that facilitates export of retroviral CTE-RNA.
abstract: The NXF1:NXT1 complex (also known as TAP:p15) is a general mRNA nuclear export factor that is conserved from yeast to humans. NXF1 is a modular protein constructed from four domains (RRM, LRR, NTF2-like and UBA domains). It is currently unclear how NXF1:NXT1 binds transcripts and whether there is higher organization of the NXF1 domains. We report here the 3.4 Å resolution crystal structure of the first three domains of human NXF1 together with NXT1 that has two copies of the complex in the asymmetric unit arranged to form an intimate domain-swapped dimer. In this dimer, the linkers between the NXF1 LRR and NTF2-like domains interact with NXT1, generating a 2-fold symmetric platform in which the RNA-binding RRM, LRR and NTF2-like domains are arranged on one face. In addition to bulk transcripts, NXF1:NXT1 also facilitates the export of unspliced retroviral genomic RNA from simple type-D retroviruses such as SRV-1 that contain a constitutive transport element (CTE), a cis-acting 2-fold symmetric RNA stem-loop motif. Complementary structural, biochemical and cellular techniques indicated that the formation of a symmetric RNA binding platform generated by dimerization of NXF1:NXT1 facilitates the recognition of CTE-RNA and promotes its nuclear export.
authors: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
authors: Shintaro
authors: S
authors: Aibara
authors: Biomolecular Networks Laboratories, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadoka, Suita, Osaka 565-0871, Japan Department of Biochemistry, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka Suita, Osaka 565-0871, Japan.
authors: Jun
authors: J
authors: Katahira
authors: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
authors: Eugene
authors: E
authors: Valkov
authors: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK ms@mrc-lmb.cam.ac.uk.
authors: Murray
authors: M
authors: Stewart
mesh_terms: D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism*; D018360:Crystallography, X-Ray; D019281:Dimerization; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D029543:Nucleocytoplasmic Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics*
chemical_list: C122111:NXF1 protein, human; C498546:NXT1 protein, human; D029543:Nucleocytoplasmic Transport Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins
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