title: Splicing factor SRSF3 represses the translation of programmed cell death 4 mRNA by associating with the 5'-UTR region.
abstract: Serine/arginine-rich splicing factor 3 (SRSF3), a member of the serine/arginine (SR)-rich family of proteins, regulates both alternative splicing of pre-mRNA and export of mature mRNA from the nucleus. Although its role in nuclear mRNA processing is well understood, the mechanism by which it alters the fate of cytoplasmic mRNA molecules remains elusive. Here, we provide evidence that SRSF3 not only regulates the alternative splicing pattern of programmed cell death 4 (PDCD4) mRNA, but also modulates its translational efficiency in the cytoplasm by lowering translation levels. We observed a marked increase in PDCD4 mRNA in translating polysome fractions upon silencing of SRSF3, and, conversely, ectopic overexpression of SRSF3 shifted PDCD4 mRNA into non-translating ribosomal fractions. In live cells, SRSF3 colocalized with PDCD4 mRNA in P-bodies (PBs), where translationally silenced mRNAs are deposited, and this localization was abrogated upon SRSF3 silencing. Furthermore, using two different reporter systems, we showed that SRSF3 interacts directly with PDCD4 mRNA and mediates translational repression by binding to the 5'-untranslated region (5'-UTR). In summary, our data suggest that the oncogenic potential of SRSF3 might be realized, in part, through the translational repression of PDCD4 mRNA.
authors.affiliation: National Research Lab for RNA Cell Biology, Department of Molecular Biology, Dankook University, Yongin, Republic of Korea.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Cellular & Molecular Medicine, College of Medicine, Chosun University, Chosun, Republic of Korea.
authors.forename: R Y
authors.initials: RY
authors.lastname: Park
authors.affiliation: Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, USA.
authors.forename: J-K
authors.initials: JK
authors.lastname: Chen
authors.affiliation: Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, USA.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.affiliation: National Research Lab for RNA Cell Biology, Department of Molecular Biology, Dankook University, Yongin, Republic of Korea.
authors.forename: S
authors.initials: S
authors.lastname: Jeong
authors.affiliation: Department of Cellular & Molecular Medicine, College of Medicine, Chosun University, Chosun, Republic of Korea.
authors.forename: T
authors.initials: T
authors.lastname: Ohn
mesh_terms: D020121:5' Untranslated Regions; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors; D014162:Transfection
chemical_list: D020121:5' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; C114487:PDCD4 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C491388:SRSF3 protein, human; D000068103:Serine-Arginine Splicing Factors