Scientific reports, 2015-09, Vol.5 (1), p.14548-14548, Article 14548
2015
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Details
- Autor(en) / Beteiligte
- Titel
- PTBP1 and PTBP2 impaired autoregulation of SRSF3 in cancer cells
- Ist Teil von
- Scientific reports, 2015-09, Vol.5 (1), p.14548-14548, Article 14548
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/srep14548Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4586487
- Format
- –
- Schlagworte
- 13/1, 13/106, 13/109, 13/89, 38/77, 631/67, 692/699, 96/31, Alternative Splicing, Base Sequence, Binding Sites, Carcinoma, Squamous Cell - genetics, Carcinoma, Squamous Cell - metabolism, Carcinoma, Squamous Cell - pathology, Codon, Terminator - metabolism, Exons, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, HEK293 Cells, Heterogeneous-Nuclear Ribonucleoproteins - genetics, Heterogeneous-Nuclear Ribonucleoproteins - metabolism, Humanities and Social Sciences, Humans, Molecular Sequence Data, Mouth Neoplasms - genetics, Mouth Neoplasms - metabolism, Mouth Neoplasms - pathology, multidisciplinary, Nerve Tissue Proteins - genetics, Nerve Tissue Proteins - metabolism, Polypyrimidine Tract-Binding Protein - genetics, Polypyrimidine Tract-Binding Protein - metabolism, Protein Binding, RNA Precursors - genetics, RNA Precursors - metabolism, RNA Stability, RNA, Messenger - genetics, RNA, Messenger - metabolism, RNA-Binding Proteins - genetics, RNA-Binding Proteins - metabolism, Science, Serine-Arginine Splicing Factors, Signal Transduction, Tissue Array Analysis, Tumor Cells, Cultured