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

<div><p>While a base substitution in intron 4 of <i>GLA</i> (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 <i>GLA</i> splicing. Amiloride, a splicing regulator in cancer cells, could reverse aberrant histone modification patterns and disrupt the association of splicing complex with <i>GLA</i>. It could also reverse aberrant <i>GLA</i> splicing in a PP1-dependant manner. Our findings revealed the alternative splicing mechanism of <i>GLA</i> (IVS4+919G>A), and a potential treatment for this specific genetic type of Fabry disease by amiloride in the future.</p></div

Additional file 2: of Long noncoding RNA TUG1 is downregulated in non-small cell lung cancer and can regulate CELF1 on binding to PRC2

RIP and DNA ChIP. (DOCX 15 kb