hnRNP L inhibits CD44 V10 exon splicing through interacting with its upstream intron.
Biochim Biophys Acta
; 1849(6): 743-50, 2015 Jun.
Article
em En
| MEDLINE
| ID: mdl-25623890
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Íntrons
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Splicing de RNA
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Receptores de Hialuronatos
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Ribonucleoproteínas Nucleares Heterogêneas Grupo L
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article