title: PTBP1 and PTBP2 impaired autoregulation of SRSF3 in cancer cells.
abstract: Splicing factors are key players in the regulation of alternative splicing of pre-mRNAs. Overexpression of splicing factors, including SRSF3, has been strongly linked with oncogenesis. However, the mechanisms behind their overexpression remain largely unclear. Autoregulation is a common mechanism to maintain relative stable expression levels of splicing factors in cells. SRSF3 regulates its own expression by enhancing the inclusion of an alternative exon 4 with an in-frame stop codon. We found that the inclusion of SRSF3 exon 4 is impaired in oral squamous cell carcinoma (OSCC) cells. PTBP1 and PTBP2 bind to an exonic splicing suppressor in exon 4 and inhibit its inclusion, which results in overexpression of full length functional SRSF3. Overexpression of SRSF3, in turn, promotes PTBP2 expression. Our results suggest a novel mechanism for the overexpression of oncogenic splicing factor via impairing autoregulation in cancer cells.
authors.affiliation: Hubei-MOST KLOS &KLOBME, School &Hospital of Stomatology, Wuhan University, Wuhan, 430079, PR China.
authors.forename: Jihua
authors.initials: J
authors.lastname: Guo
authors.affiliation: Hubei-MOST KLOS &KLOBME, School &Hospital of Stomatology, Wuhan University, Wuhan, 430079, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jia
authors.affiliation: Hubei-MOST KLOS &KLOBME, School &Hospital of Stomatology, Wuhan University, Wuhan, 430079, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Jia
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D001665:Binding Sites; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018388:Codon, Terminator / Q000378:metabolism; D005091:Exons; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D015398:Signal Transduction; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured
chemical_list: D018388:Codon, Terminator; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009419:Nerve Tissue Proteins; C450006:PTBP1 protein, human; C504334:PTBP2 protein, human; D012322:RNA Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C491388:SRSF3 protein, human; D038941:Polypyrimidine Tract-Binding Protein; D000068103:Serine-Arginine Splicing Factors