The Skipping of Constitutive Exons in Vivo Induced by Nonsense Mutations

TLDR

Nonsense mutations introduce premature stop codons that often reduce mutant transcript levels or produce truncated proteins. In patients with Marfan syndrome and gyrate atrophy, nonsense mutations caused skipping of constitutive exons, and unchanged flanking splice sites indicate that such mutations can alter splice site selection in vivo.

Abstract

Nonsense mutations create a premature signal for the termination of translation of messenger RNA. Such mutations have been observed to cause a severe reduction in the amount of mutant allele transcript or to generate a peptide truncated at the carboxyl end. Analysis of fibrillin transcript from a patient with Marfan syndrome revealed the skipping of a constitutive exon containing a nonsense mutation. Similar results were observed for two nonsense mutations in the gene encoding ornithine δ-aminotransferase from patients with gyrate atrophy. All genomic DNA sequences flanking these exons that are known to influence RNA splicing were unaltered, which suggests that nonsense mutations can alter splice site selection in vivo.