title: Serine/arginine-rich protein 30c activates human papillomavirus type 16 L1 mRNA expression via a bimodal mechanism.
abstract: Two splice sites on the human papillomavirus type 16 (HPV-16) genome are used exclusively by the late capsid protein L1 mRNAs: SD3632 and SA5639. These splice sites are suppressed in mitotic cells. This study showed that serine/arginine-rich protein 30c (SRp30c), also named SFRS9, activated both SD3632 and SA5639 and induced production of L1 mRNA. Activation of HPV-16 L1 mRNA splicing by SRp30c required an intact arginine/serine-repeat (RS) domain of SRp30c. In addition to this effect, SRp30c could enhance L1 mRNA production indirectly by inhibiting the early 3'-splice site SA3358, which competed with the late 3'-splice site SA5639. SRp30c bound directly to sequences downstream of SA3358, suggesting that SRp30c inhibited the enhancer at SA3358 and caused a redirection of splicing to the late 3'-splice site SA5639. This inhibitory effect of SRp30c was independent of its RS domain. These results suggest that SRp30c can activate HPV-16 L1 mRNA expression via a bimodal mechanism: directly by stimulating splicing to late splice sites and indirectly by inhibiting competing early splice sites.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Biomedical Center, Husargatan 3, Box 582, 751 23 Uppsala, Sweden.
authors.forename: Monika
authors.initials: M
authors.lastname: Somberg
authors.affiliation: Department of Laboratory Medicine, Section of Medical Microbiology, Lund University, 221 84 Lund, Sweden.|Department of Medical Biochemistry and Microbiology, Uppsala University, Biomedical Center, Husargatan 3, Box 582, 751 23 Uppsala, Sweden.
authors.forename: Xiaoze
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Biomedical Center, Husargatan 3, Box 582, 751 23 Uppsala, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Johansson
authors.affiliation: Dublin Institute of Technology, Kevin Street, Dublin 8, Ireland.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Orru
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Biomedical Center, Husargatan 3, Box 582, 751 23 Uppsala, Sweden.
authors.forename: Roger
authors.initials: R
authors.lastname: Chang
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Biomedical Center, Husargatan 3, Box 582, 751 23 Uppsala, Sweden.
authors.forename: Margaret
authors.initials: M
authors.lastname: Rush
authors.affiliation: Dublin Institute of Technology, Kevin Street, Dublin 8, Ireland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Fay
authors.affiliation: Dublin Institute of Technology, Kevin Street, Dublin 8, Ireland.
authors.forename: Fergus
authors.initials: F
authors.lastname: Ryan
authors.affiliation: Dublin Institute of Technology, Kevin Street, Dublin 8, Ireland.|Department of Laboratory Medicine, Section of Medical Microbiology, Lund University, 221 84 Lund, Sweden.|Department of Medical Biochemistry and Microbiology, Uppsala University, Biomedical Center, Husargatan 3, Box 582, 751 23 Uppsala, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwartz
mesh_terms: D036022:Capsid Proteins / Q000096:biosynthesis*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors
chemical_list: D036022:Capsid Proteins; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000068103:Serine-Arginine Splicing Factors; C063317:L1 protein, Human papillomavirus type 16