title: Truncated serine/arginine-rich splicing factor 3 accelerates cell growth through up-regulating c-Jun expression.
abstract: Serine/arginine-rich splicing factor 3 (SRSF3), a member of the SRSF family, plays a wide-ranging role in gene expression. The human SRSF3 gene generates a major mRNA isoform encoding a functional, full-length protein and a PTC-containing isoform (SRSF3-PTC). The latter is expected to be degraded through the nonsense-mediated mRNA decay system. However, it was reported that SRSF3-PTC mRNA was produced under stressful conditions and translated into a truncated SRSF3 protein (SRSF3-TR). To disclose unknown functions of SRSF3-TR, we established Flp-In-293 cells stably expressing SRSF3-TR. The SRSF3-TR-expressing cells increased mRNA and protein levels of positive regulators for G1 to S phase transition (cyclin D1, cyclin D3, CDC25A, and E2F1) and accelerated their growth. c-Jun is required for progression through the G1 phase, the mechanism by which involves transcriptional control of the cyclin D1 gene. We also found that the JUN promoter activity was significantly increased in the Flp-In-293 cells stably expressing SRSF3-TR, compared with mock-transfected control cells. The SRSF3-TR-expressing cells increased c-Jun and Sp-1 levels, which are important for the positive autoregulation and basal transcription of JUN, respectively. Our results suggest that stress-inducible SRSF3-TR may participate in the acceleration of cell growth through facilitating c-Jun-mediated G1 progression under stressful conditions.
authors.affiliation: Department of Stress Science, Institute of Health Biosciences, the University of Tokushima Graduate School.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Kano
authors.forename: Kensei
authors.initials: K
authors.lastname: Nishida
authors.forename: Chihiro
authors.initials: C
authors.lastname: Nishiyama
authors.forename: Yoko
authors.initials: Y
authors.lastname: Akaike
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kajita
authors.forename: Ken
authors.initials: K
authors.lastname: Kurokawa
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Masuda
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kuwano
authors.forename: Toshihito
authors.initials: T
authors.lastname: Tanahashi
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Rokutan
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D002460:Cell Line; D049109:Cell Proliferation; D004247:DNA / Q000235:genetics; D059585:G1 Phase Cell Cycle Checkpoints; D019940:Genes, bcl-1; D016758:Genes, jun; D006801:Humans; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D015854:Up-Regulation
chemical_list: D010446:Peptide Fragments; D016601:RNA-Binding Proteins; C491388:SRSF3 protein, human; D000068103:Serine-Arginine Splicing Factors; D004247:DNA