2. Academic Validation
  3. hnRNP L inhibits CD44 V10 exon splicing through interacting with its upstream intron

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.
Tiing Jen Loh 1,  Sunghee Cho 1,  Heegyum Moon 1,  Ha Na Jang 1,  Darren Reece Williams 1,  Da-Woon Jung 1,  Il-Chul Kim 2,  Claudia Ghigna 3,  Giuseppe Biamonti 3,  Xuexiu Zheng 1,  Haihong Shen 4
Affiliations

Affiliations

  • 1 School of life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
  • 2 Department of Biological Sciences, Chonnam National University, Gwangju 500-757, Republic of Korea.
  • 3 Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, 27100 Pavia, Italy.
  • 4 School of life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea. Electronic address: [email protected].
PMID: 25623890 DOI: 10.1016/j.bbagrm.2015.01.004
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.

Keywords

CD44; Pre-mRNA splicing; V(10) exon; hnRNP L.

Figures