title: Two isoforms of the T-cell intracellular antigen 1 (TIA-1) splicing factor display distinct splicing regulation activities. Control of TIA-1 isoform ratio by TIA-1-related protein.
abstract: TIA-1 (T-cell Intracellular Antigen 1) and TIAR (TIA-1-related protein) are RNA-binding proteins involved in the regulation of alternative pre-mRNA splicing and other aspects of RNA metabolism. Various isoforms of these proteins exist in mammals. For example, TIA-1 presents two major isoforms (TIA-1a and TIA-1b) generated by alternative splicing of exon 5 that differ by eleven amino acids exclusive of the TIA-1a isoform. Here we show that the relative expression of TIA-1 and TIAR isoforms varies in different human tissues and cell lines, suggesting distinct functional properties and regulated isoform expression. We report that whereas TIA-1 isoforms show similar subcellular distribution and RNA binding, TIA-1b displays enhanced splicing stimulatory activity compared with TIA-1a, both in vitro and in vivo. Interestingly, TIAR depletion from HeLa and mouse embryonic fibroblasts results in an increased ratio of TIA-1b/a expression, suggesting that TIAR regulates the relative expression of TIA-1 isoforms. Taken together, the results reveal distinct functional properties of TIA-1 isoforms and the existence of a regulatory network that controls isoform expression.
authors.affiliation: Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain. jmizquierdo@cbm.uam.es
authors.forename: José M
authors.initials: JM
authors.lastname: Izquierdo
authors.forename: Juan
authors.initials: J
authors.lastname: Valcárcel
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D039102:Poly(A)-Binding Proteins / Q000096:biosynthesis*; D020033:Protein Isoforms / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D051381:Rats; D000074019:T-Cell Intracellular Antigen-1
chemical_list: D039102:Poly(A)-Binding Proteins; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; C499367:Tia1 protein, mouse; C489665:Tial1 protein, mouse; C489666:Tial1 protein, rat; C076751:TIAL1 protein, human