Blocking the 5' splice site of exon 4 by a morpholino oligomer triggers APOL1 protein isoform switch.

ABSTRACT: APOL1 risk alleles G1 or G2 are associated with a kidney disease phenotype exclusively in people of recent African ancestry. Here we show that exon 4 encoding a part of the APOL1 signal peptide is constitutively spliced in major APOL1 transcripts expressed in kidney glomerular and tubular cells. We demonstrate that constitutive splicing of exon 4 results from a suboptimal hnRNP A1 binding motif found in exon 4. Accordingly, a robust binding of hnRNP A1 protein to a consensus hnRNP A1 cis-acting element in exon 4 results in almost complete exclusion of exon 4 from the APOL1 minigene transcripts. Blocking the 5' splice site at the exon 4/intron boundary with a specific antisense morpholino oligonucleotide excludes exon 4 from the splicing pattern of endogenous APOL1 transcripts. These transc

SUBMITTER: Cheatham AM 

PROVIDER: S-EPMC5992166 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature