title: SRSF3 represses the expression of PDCD4 protein by coordinated regulation of alternative splicing, export and translation.
abstract: Gene expression is regulated at multiple steps, such as transcription, splicing, export, degradation and translation. Considering diverse roles of SR proteins, we determined whether the tumor-related splicing factor SRSF3 regulates the expression of the tumor-suppressor protein, PDCD4, at multiple steps. As we have reported previously, knockdown of SRSF3 increased the PDCD4 protein level in SW480 colon cancer cells. More interestingly, here we showed that the alternative splicing and the nuclear export of minor isoforms of pdcd4 mRNA were repressed by SRSF3, but the translation step was unaffected. In contrast, only the translation step of the major isoform of pdcd4 mRNA was repressed by SRSF3. Therefore, overexpression of SRSF3 might be relevant to the repression of all isoforms of PDCD4 protein levels in most types of cancer cell. We propose that SRSF3 could act as a coordinator of the expression of PDCD4 protein via two mechanisms on two alternatively spliced mRNA isoforms.
authors.affiliation: Department of Molecular Biology, Dankook University, Yongin, Gyeonggi-do, Republic of Korea.
authors.forename: Seung Kuk
authors.initials: SK
authors.lastname: Park
authors.affiliation: Department of Molecular Biology, Dankook University, Yongin, Gyeonggi-do, Republic of Korea. Electronic address: sjsj@dankook.ac.kr.
authors.forename: Sunjoo
authors.initials: S
authors.lastname: Jeong
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D014176:Protein Biosynthesis / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; C491388:SRSF3 protein, human; D000068103:Serine-Arginine Splicing Factors
keywords: Alterative splicing; Export; PDCD4; SRSF3; Translation