title: An NXF1 mRNA with a retained intron is expressed in hippocampal and neocortical neurons and is translated into a protein that functions as an Nxf1 cofactor.
abstract: The Nxf1 protein is a major nuclear export receptor for the transport of mRNA, and it also is essential for export of retroviral mRNAs with retained introns. In the latter case, it binds to RNA elements known as constitutive transport elements (CTEs) and functions in conjunction with a cofactor known as Nxt1. The NXF1 gene also regulates expression of its own intron-containing RNA through the use of a functional CTE within intron 10. mRNA containing this intron is exported to the cytoplasm, where it can be translated into the 356-amino acid short Nxf1(sNxf1) protein, despite the fact that it is a prime candidate for nonsense-mediated decay (NMD). Here we demonstrate that sNxf1 is highly expressed in nuclei and dendrites of hippocampal and neocortical neurons in rodent brain. Additionally, we show that sNxf1 localizes in RNA granules in neurites of differentiated N2a mouse neuroblastoma cells, where it shows partial colocalization with Staufen2 isoform SS, a protein known to play a role in dendritic mRNA trafficking. We also show that sNxf1 forms heterodimers in conjunction with the full-length Nxf1 and that sNxf1 can replace Nxt1 to enhance the expression of CTE-containing mRNA and promote its association with polyribosomes.
authors.affiliation: Myles H. Thaler Center for AIDS and Human Retrovirus Research and Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22908.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Myles H. Thaler Center for AIDS and Human Retrovirus Research and Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22908.
authors.forename: Yeou-Cherng
authors.initials: YC
authors.lastname: Bor
authors.affiliation: Departments of Neuroscience and Neurosurgery, University of Virginia School of Medicine, Charlottesville, VA 22908.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Fitzgerald
authors.affiliation: Departments of Neuroscience and Neurosurgery, University of Virginia School of Medicine, Charlottesville, VA 22908.
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Myles H. Thaler Center for AIDS and Human Retrovirus Research and Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22908.
authors.forename: David
authors.initials: D
authors.lastname: Rekosh
authors.affiliation: Myles H. Thaler Center for AIDS and Human Retrovirus Research and Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22908 mh7g@virginia.edu.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Hammarskjold
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D017398:Alternative Splicing; D000818:Animals; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism; D007438:Introns; D051379:Mice; D019579:Neocortex / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism*; D011132:Polyribosomes / Q000378:metabolism; D059368:RNA Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism
chemical_list: C569386:NXF1 protein, mouse; D009419:Nerve Tissue Proteins; D029543:Nucleocytoplasmic Transport Proteins; D059368:RNA Isoforms; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C471845:stau2 protein, mouse