Aberrant splicing of the IVS1 + 5 G>A mutated human β-globin results in 2 potential NMD substrates.

Structure of human β-globin pre-mRNAs and mature mRNAs resulting from splicing at the normal splice site and at 3 cryptic splice sites at positions −38 nts, −16 nts, and +12 nts (arrows) relative to the normal intron 1 splice donor. The ORFs of the −16 and −38 transcripts are phase-shifted at the respective intron 1 splice sites, and translation terminates at PTC 55* and at PTC 30* in exon 2, respectively. In contrast, the +12 transcript is extended by 12 nts and translation terminates at the normal stop codon. The 5′UTR of the mRNAs contains an IRE that confers a specific regulation of translation under conditions of iron depletion and repletion.