title: Differential isoform expression and interaction with the P32 regulatory protein controls the subcellular localization of the splicing factor U2AF26.
abstract: The U2 auxiliary factor (U2AF) is an integral part of the spliceosome that is important for the recognition of the 3' splice site. U2AF consists of a large and a small subunit, the prototypes of which are U2AF65 and U2AF35. Recent evidence suggests that several homologs of both U2AF subunits exist that are able to regulate alternative splicing. Here we have investigated the expression, intracellular localization, and nucleo-cytoplasmic shuttling of one homolog of the small U2AF subunit, U2AF26, and a splice variant lacking exon 7, U2AF26DeltaE7. In contrast to the nuclear U2AF26, which displays active nucleo-cytoplasmic shuttling, U2AF26DeltaE7 is localized in the cytoplasm. Our studies reveal a nuclear localization sequence in the C-terminal exons 7 and 8 of U2AF26 that differs from the known nuclear localization sequence in U2AF35. In addition, we could identify P32 as a protein that is able to interact with U2AF26 through this domain, and we demonstrate that this interaction is required for the nuclear translocation of U2AF26. Our results suggest the existence of two distinct nuclear import pathways for U2AF26 and U2AF35 that could independently control their intracellular distribution and availability to the splicing machinery. Such a mechanism could work in addition to the differential expression of U2AF homologs to contribute to the regulation of alternative splicing.
authors.affiliation: Institut de Recherches Cliniques de Montréal, Montréal, Quebec H2W 1R7, Canada.
authors.forename: Florian
authors.initials: F
authors.lastname: Heyd
authors.forename: Maria
authors.initials: M
authors.lastname: Carmo-Fonseca
authors.forename: Tarik
authors.initials: T
authors.lastname: Möröy
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D022821:RNA Splice Sites / Q000502:physiology; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D017381:Spliceosomes / Q000235:genetics / Q000378:metabolism; D000072668:Splicing Factor U2AF
chemical_list: C087299:C1QBP protein, human; C490193:C1qbp protein, mouse; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D022821:RNA Splice Sites; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; C076753:U2AF1 protein, human; C000607494:U2AF2 protein, human; C443672:U2af1l4 protein, mouse; C000607495:Zrsr1 protein, mouse