HnRNP L inhibits CD44 V10 exon splicing through interacting with its upstream intron

Tiing Jen Loh, Sunghee Cho, Heegyum Moon, Ha Na Jang, Darren Reece Williams, Da Woon Jung, Il Chul Kim, Claudia Ghigna, Giuseppe Biamonti, Xuexiu Zheng, Haihong Shen

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15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)743-750
Number of pages8
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1849
Issue number6
DOIs
Publication statusPublished - 15 May 2015
Externally publishedYes

Keywords

  • CD44
  • HnRNP L
  • Pre-mRNA splicing
  • V exon

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