title: Phosphorylation-dependent and -independent nuclear import of RS domain-containing splicing factors and regulators.
abstract: SR proteins and related RS domain-containing polypeptides are an important class of splicing regulators in higher eukaryotic cells. The RS domain facilitates nuclear import of SR proteins and mediates protein-protein interactions during spliceosome assembly; both functions appear to subject to regulation by phosphorylation. Previous studies have identified two nuclear import receptors for SR proteins, transportin-SR1 and transportin-SR2. Here we show that transportin-SR1 and transportin-SR2 are the alternatively spliced products of the same gene and that transportin-SR2 is the predominant transcript in most cells and tissues examined. While both receptors import typical SR proteins in a phosphorylation-dependent manner, they differentially import the RS domain-containing splicing regulators hTra2alpha and hTra2beta in different phosphorylation states. We suggest that differential regulation of nuclear import may serve as a mechanism for homeostasis of RS domain-containing splicing factors and regulators in the nucleus and for selective cellular responses to signaling.
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0651, USA.
authors.forename: Chi Y
authors.initials: CY
authors.lastname: Yun
authors.forename: Adolfo L
authors.initials: AL
authors.lastname: Velazquez-Dones
authors.forename: Susan K
authors.initials: SK
authors.lastname: Lyman
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Fu
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005914:Globins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000737:chemistry*; D008954:Models, Biological; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012326:RNA Splicing; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014018:Tissue Distribution; D028961:beta Karyopherins / Q000737:chemistry*
chemical_list: D028884:Karyopherins; D011994:Recombinant Proteins; D028961:beta Karyopherins; C424165:transportin SR2; D005914:Globins; D005978:Glutathione