Modulation the alternative splicing of GLA (IVS4+919G>A) in Fabry disease

Wen Hsin Chang, Dau Ming Niu, Chi Yu Lu, Shyr Yi Lin, Ta Chih Liu, Jan Gowth Chang

Research output: Contribution to journalArticle

6 Citations (Scopus)


While a base substitution in intron 4 of GLA (IVS4+919G>A) that causes aberrant alternative splicing resulting in Fabry disease has been reported, its molecular mechanism remains unclear. Here we reported that upon IVS4+919G>A transversion, H3K36me3 was enriched across the alternatively spliced region. PSIP1, an adapter of H3K36me3, together with Hsp70 and NONO were recruited and formed a complex with SF2/ASF and SRp20, which further promoted GLA splicing. Amiloride, a splicing regulator in cancer cells, could reverse aberrant histone modification patterns and disrupt the association of splicing complex with GLA. It could also reverse aberrant GLA splicing in a PP1-dependant manner. Our findings revealed the alternative splicing mechanism of GLA (IVS4+919G>A), and a potential treatment for this specific genetic type of Fabry disease by amiloride in the future.

Original languageEnglish
Article numbere0175929
JournalPLoS One
Issue number4
Publication statusPublished - Apr 1 2017

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Chang, W. H., Niu, D. M., Lu, C. Y., Lin, S. Y., Liu, T. C., & Chang, J. G. (2017). Modulation the alternative splicing of GLA (IVS4+919G>A) in Fabry disease. PLoS One, 12(4), [e0175929].