hnRNP L inhibits CD44 V10 exon splicing through interacting with its upstream intron.
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Loh TJ, Cho S, Moon H, Jang HN, Williams DR, Jung DW, Kim IC, Ghigna C, Biamonti G, Zheng X, Shen H
hnRNP L inhibits CD44 V10 exon splicing through interacting with its upstream intron.
Biochim Biophys Acta. 2015 Jun;1849(6):743-50. doi: 10.1016/j.bbagrm.2015.01.004. Epub 2015 Jan 24.
- PubMed ID
- 25623890 [ View in PubMed]
- 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.