title: SRSF2 promotes splicing and transcription of exon 11 included isoform in Ron proto-oncogene.
abstract: The product of proto-oncogene Ron is a human receptor for the macrophage-stimulating protein (MSP). Upon activation, Ron is able to induce cell dissociation, migration and matrix invasion. Exon 11 skipping of Ron pre-mRNA produces Ron△165 protein that is constitutively active even in the absence of its ligand. Here we show that knockdown of SRSF2 promotes the decrease of exon 11 inclusion, whereas overexpression of SRSF2 promotes exon 11 inclusion. We demonstrate that SRSF2 promotes exon 11 inclusion through splicing and transcription procedure. We also present evidence that reduced expression of SRSF2 induces a decrease in the splicing of both introns 10 and 11; by contrast, overexpression of SRSF2 induces an increase in the splicing of introns 10 and 11. Through mutation analysis, we show that SRSF2 functionally targets and physically interacts with CGAG sequence on exon 11. In addition, we reveal that the weak strength of splice sites of exon 11 is not required for the function of SRSF2 on the splicing of Ron exon 11. Our results indicate that SRSF2 promotes exon 11 inclusion of Ron proto-oncogene through targeting exon 11. Our study provides a novel mechanism by which Ron is expressed.
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Heegyum
authors.initials: H
authors.lastname: Moon
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Sunghee
authors.initials: S
authors.lastname: Cho
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Tiing Jen
authors.initials: TJ
authors.lastname: Loh
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Oh
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Ha Na
authors.initials: HN
authors.lastname: Jang
authors.affiliation: JiangSu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Bioscience & Biotechnology, Sejong University, Seoul 143-747, Republic of Korea.
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Kwon
authors.affiliation: Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: D Joshua
authors.initials: DJ
authors.lastname: Liao
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Jun
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Soohyun
authors.initials: S
authors.lastname: Eom
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, 27100 Pavia, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ghigna
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, 27100 Pavia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biamonti
authors.affiliation: Howard Hughes Medical Institute and Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Green
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Xuexiu
authors.initials: X
authors.lastname: Zheng
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea. Electronic address: haihongshen@gist.ac.kr.
authors.forename: Haihong
authors.initials: H
authors.lastname: Shen
mesh_terms: D002478:Cells, Cultured; D005091:Exons / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000235:genetics; D012326:RNA Splicing; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012261:Ribonucleoproteins / Q000502:physiology*; D000068103:Serine-Arginine Splicing Factors; D014158:Transcription, Genetic
chemical_list: D007527:Isoenzymes; C000715470:MAS1 protein, human; D009687:Nuclear Proteins; D000090063:Proto-Oncogene Mas; D012261:Ribonucleoproteins; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases
keywords: Exon 11 inclusion; Pre-mRNA splicing; Proto-oncogene; Ron; SRSF2; Transcription