title: A genome landscape of SRSF3-regulated splicing events and gene expression in human osteosarcoma U2OS cells.
abstract: Alternative RNA splicing is an essential process to yield proteomic diversity in eukaryotic cells, and aberrant splicing is often associated with numerous human diseases and cancers. We recently described serine/arginine-rich splicing factor 3 (SRSF3 or SRp20) being a proto-oncogene. However, the SRSF3-regulated splicing events responsible for its oncogenic activities remain largely unknown. By global profiling of the SRSF3-regulated splicing events in human osteosarcoma U2OS cells, we found that SRSF3 regulates the expression of 60 genes including ERRFI1, ANXA1 and TGFB2, and 182 splicing events in 164 genes, including EP300, PUS3, CLINT1, PKP4, KIF23, CHK1, SMC2, CKLF, MAP4, MBNL1, MELK, DDX5, PABPC1, MAP4K4, Sp1 and SRSF1, which are primarily associated with cell proliferation or cell cycle. Two SRSF3-binding motifs, CCAGC(G)C and A(G)CAGCA, are enriched to the alternative exons. An SRSF3-binding site in the EP300 exon 14 is essential for exon 14 inclusion. We found that the expression of SRSF1 and SRSF3 are mutually dependent and coexpressed in normal and tumor tissues/cells. SRSF3 also significantly regulates the expression of at least 20 miRNAs, including a subset of oncogenic or tumor suppressive miRNAs. These data indicate that SRSF3 affects a global change of gene expression to maintain cell homeostasis.
authors.affiliation: Tumor Virus RNA Biology Section, Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ajiro
authors.affiliation: Tumor Virus RNA Biology Section, Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Jia
authors.affiliation: DNA Sequencing and Genomics Core, System Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: DNA Sequencing and Genomics Core, System Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Tumor Virus RNA Biology Section, Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA zhengt@exchange.nih.gov.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Zheng
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D040901:Proteomics; D000090063:Proto-Oncogene Mas; D012326:RNA Splicing / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D000068103:Serine-Arginine Splicing Factors
chemical_list: C000715470:MAS1 protein, human; D035683:MicroRNAs; D000090063:Proto-Oncogene Mas; D016601:RNA-Binding Proteins; C491388:SRSF3 protein, human; D000068103:Serine-Arginine Splicing Factors