title: hnRNP L inhibits CD44 V10 exon splicing through interacting with its upstream intron.
abstract: CD44 is a complex cell adhesion molecule that mediates communication and adhesion between adjacent cells as well as between cells and the extracellular matrix. CD44 pre-mRNA produces various mRNA isoforms through alternative splicing of 20 exons, among which exons 1-5 (C1-C5) and 16-20 (C6-C10) are constant exons, whereas exons 6-15 (V1-V10) are variant exons. CD44 V10 exon has important roles in breast tumor progression and Hodgkin lymphoma. Here we show that increased expression of hnRNP L inhibits V10 exon splicing of CD44 pre-mRNA, whereas reduced expression of hnRNP L promotes V10 exon splicing. In addition, hnRNP L also promotes V10 splicing of endogenous CD44 pre-mRNA. Through mutation analysis, we demonstrate that the effects of hnRNP L on V10 splicing are abolished when the CA-rich sequence on the upstream intron of V10 exon is disrupted. However, hnRNP L effects are stronger if more CA-repeats are provided. Furthermore, we show that hnRNP L directly contacts the CA-rich sequence. Importantly, we provide evidences that hnRNP L inhibits U2AF65 binding on the upstream Py tract of V10 exon. Our results reveal that hnRNP L is a new regulator for CD44 V10 exon 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.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: 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: Ha Na
authors.initials: HN
authors.lastname: Jang
authors.affiliation: School of life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Darren Reece
authors.initials: DR
authors.lastname: Williams
authors.affiliation: School of life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Da-Woon
authors.initials: DW
authors.lastname: Jung
authors.affiliation: Department of Biological Sciences, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Il-Chul
authors.initials: IC
authors.lastname: Kim
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: 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: D002448:Cell Adhesion / Q000235:genetics; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation; D006367:HeLa Cells; D034664:Heterogeneous-Nuclear Ribonucleoprotein L / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000378:metabolism; D007438:Introns / Q000235:genetics*; D009687:Nuclear Proteins / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics*; D012261:Ribonucleoproteins / Q000378:metabolism; D000072668:Splicing Factor U2AF
chemical_list: C497483:CD44 protein, human; D034664:Heterogeneous-Nuclear Ribonucleoprotein L; D018960:Hyaluronan Receptors; D009687:Nuclear Proteins; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; C000607494:U2AF2 protein, human
keywords: CD44; Pre-mRNA splicing; V(10) exon; hnRNP L