title: Evolutionary conservation of a molecular machinery for export and expression of mRNAs with retained introns.
abstract: Intron retention is one of the least studied forms of alternative splicing. Through the use of retrovirus and other model systems, it was established many years ago that mRNAs with retained introns are subject to restriction both at the level of nucleocytoplasmic export and cytoplasmic expression. It was also demonstrated that specific cis-acting elements in the mRNA could serve to bypass these restrictions. Here we show that one of these elements, the constitutive transport element (CTE), first identified in the retrovirus MPMV and subsequently in the human NXF1 gene, is a highly conserved element. Using GERP analysis, CTEs with strong primary sequence homology, predicted to display identical secondary structure, were identified in NXF genes from >30 mammalian species. CTEs were also identified in the predicted NXF1 genes of zebrafish and coelacanths. The CTE from the zebrafish NXF1 was shown to function efficiently to achieve expression of mRNA with a retained intron in human cells in conjunction with zebrafish Nxf1 and cofactor Nxt proteins. This demonstrates that all essential functional components for expression of mRNA with retained introns have been conserved from fish to man.
authors.affiliation: Myles H. Thaler Center for AIDS and Human Retrovirus Research, Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: Baomin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Myles H. Thaler Center for AIDS and Human Retrovirus Research, Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: David
authors.initials: D
authors.lastname: Rekosh
authors.affiliation: Myles H. Thaler Center for AIDS and Human Retrovirus Research, Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA mh7g@virginia.edu.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Hammarskjold
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D017124:Conserved Sequence; D003593:Cytoplasm / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D007438:Introns / Q000235:genetics*; D008322:Mammals; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D015027:Zebrafish
chemical_list: C122111:NXF1 protein, human; D029543:Nucleocytoplasmic Transport Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins
keywords: CTE; RNA export; conserved RNA element; intron retention; post-transcriptional gene regulation