title: SC35 promotes splicing of the C5-V6-C6 isoform of CD44 pre-mRNA.
abstract: CD44 is a cell membrane glycoprotein that mediates the response of cells to their cellular microenvironment and regulates growth, survival, differentiation and motility. CD44 pre-mRNA contains 20 exons, 10 of which are alternatively spliced. Among the CD44 spliced variants, one of the V6 exon-containing isoforms, the V4-7 variant which contains variable exons 4, 5, 6 and 7, confers metastatic potential to non-metastatic cells. However, the splicing regulation of the V6 exon is not completely understood. SC35 is an arginine-serine rich protein that regulates alternative splicing of various pre-mRNAs. In the present study, we established a stable cell line which indicates inclusion or skipping of the V6 exon with the RFP or GFP signal. Using this stable cell line, we found that the V6 exon and flanking introns of CD44 pre-mRNA contained SC35 response elements that regulate V6 splicing. RT-PCR analyses of the endogenous CD44 splicing showed that SC35 promotes the production of the C5-V6-C6 isoform. shRNA knockdown of SC35 showed that reduced expression of SC35 decreased expression of the V6 exon-containing isoforms. Our results reveal a novel mechanism of CD44V6 splicing.
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.forename: Heegyum
authors.initials: H
authors.lastname: Moon
authors.forename: Sunghee
authors.initials: S
authors.lastname: Cho
authors.forename: Da-Woon
authors.initials: DW
authors.lastname: Jung
authors.forename: Seong-Eui
authors.initials: SE
authors.lastname: Hong
authors.forename: Do Han
authors.initials: DH
authors.lastname: Kim
authors.forename: Michael R
authors.initials: MR
authors.lastname: Green
authors.forename: Xuexiu
authors.initials: X
authors.lastname: Zheng
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhou
authors.forename: Haihong
authors.initials: H
authors.lastname: Shen
mesh_terms: D017398:Alternative Splicing; D045744:Cell Line, Tumor; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D061986:MCF-7 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics; D034622:RNA Interference; D012322:RNA Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering; D012261:Ribonucleoproteins / Q000235:genetics / Q000502:physiology*; D000068103:Serine-Arginine Splicing Factors
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012322:RNA Precursors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012261:Ribonucleoproteins; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors