Cystic fibrosis transmembrane conductance regulator (CFTR) mRNA containing premature termination codons (CFTR mRNA (PTC))

Cystic fibrosis transmembrane conductance regulator (CFTR) mRNA transcripts containing premature termination codons (PTCs) are the molecular products of nonsense mutations in the CFTR gene, such as G542X or W1282X (PMID: 31433984). These transcripts are typically recognized and degraded by the cellular nonsense-mediated mRNA decay (NMD) pathway, which prevents the synthesis of truncated proteins but also results in a near-total absence of functional CFTR protein (PMID: 29133708). The lack of functional CFTR, a cAMP-regulated chloride channel, leads to dehydrated airway surface liquid and the characteristic thick mucus of cystic fibrosis (PMID: 30535111). Therapeutic interventions targeting these transcripts include translational read-through agents like ataluren and ELX-02, which facilitate the insertion of a near-cognate amino acid at the PTC site to produce full-length protein (PMID: 30143556). Additionally, NMD inhibitors are being investigated to stabilize these mRNA transcripts, thereby increasing the pool of substrate available for read-through drugs to act upon (PMID: 28430615). This dual approach aims to restore enough CFTR function to alleviate the clinical symptoms of the disease (PMID: 24630181).

Other names

Nonsense-mutated CFTR mRNAPTC-containing CFTR mRNACFTR mRNA with premature stop codons

Induction of translational read-through at premature termination codons and inhibition of nonsense-mediated mRNA decay