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: Jihua Guo, Jun Jia, Rong Jia
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 14548 (Sep 29 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26416554 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Codon, Terminator
• Heterogeneous-Nuclear Ribonucleoproteins
• Nerve Tissue Proteins
• PTBP1 protein, human
• PTBP2 protein, human
• RNA Precursors
• RNA, Messenger
• RNA-Binding Proteins
• SRSF3 protein, human
• Polypyrimidine Tract-Binding Protein
• Serine-Arginine Splicing Factors

Topics

• Alternative Splicing
• Base Sequence
• Binding Sites
• Carcinoma, Squamous Cell (genetics, metabolism, pathology)
• Codon, Terminator (metabolism)
• Exons
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• HEK293 Cells
• Heterogeneous-Nuclear Ribonucleoproteins (genetics, metabolism)
• Humans
• Molecular Sequence Data
• Mouth Neoplasms (genetics, metabolism, pathology)
• Nerve Tissue Proteins (genetics, metabolism)
• Polypyrimidine Tract-Binding Protein (genetics, metabolism)
• Protein Binding
• RNA Precursors (genetics, metabolism)
• RNA Stability
• RNA, Messenger (genetics, metabolism)
• RNA-Binding Proteins (genetics, metabolism)
• Serine-Arginine Splicing Factors
• Signal Transduction
• Tissue Array Analysis
• Tumor Cells, Cultured