Differential Isoform Expression and Interaction with the P32 Regulatory Protein Controls the Subcellular Localization of the Splicing Factor U2AF26
Copyright policy )Differential Isoform Expression and Interaction with the P32 Regulatory Protein Controls the Subcellular Localization of the Splicing Factor U2AF26
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.
- Gulbenkian Institute for Molecular Medicine Portugal
- University of Lisbon Portugal
- Montreal Clinical Research Institute Canada
- INSTITUTO DE MEDICINA MOLECULAR Portugal
- University of Montreal Canada
Cell Nucleus, Cytoplasm, Active Transport, Cell Nucleus, Nuclear Proteins, Protein Structure, Tertiary, Mitochondrial Proteins, Alternative Splicing, Mice, Hyaluronan Receptors, Ribonucleoproteins, COS Cells, Chlorocebus aethiops, NIH 3T3 Cells, Spliceosomes, Animals, Humans, Protein Isoforms, RNA Splice Sites, Carrier Proteins, HeLa Cells
Cell Nucleus, Cytoplasm, Active Transport, Cell Nucleus, Nuclear Proteins, Protein Structure, Tertiary, Mitochondrial Proteins, Alternative Splicing, Mice, Hyaluronan Receptors, Ribonucleoproteins, COS Cells, Chlorocebus aethiops, NIH 3T3 Cells, Spliceosomes, Animals, Humans, Protein Isoforms, RNA Splice Sites, Carrier Proteins, HeLa Cells
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