Polyadenylate-binding protein nuclear 1 mRNA (PABPN1 mRNA)

Polyadenylate-binding protein nuclear 1 (PABPN1) mRNA encodes a protein essential for the polyadenylation of pre-mRNAs, a process that stabilizes transcripts and facilitates their export from the nucleus (UniProt Q86U42). Mutations in the PABPN1 gene, specifically an expansion of the GCN trinucleotide repeat, result in a polyalanine-expanded protein that forms toxic intranuclear inclusions in skeletal muscle (NIH GARD). This molecular pathology underlies Oculopharyngeal Muscular Dystrophy (OPMD), a late-onset disease characterized by progressive swallowing difficulties and eyelid drooping (PubMed 28344313). Because PABPN1 is essential for cell survival, therapeutic strategies targeting the mRNA typically utilize a silence and replace approach. This involves using RNA interference (RNAi) to degrade the endogenous PABPN1 mRNA while simultaneously introducing a codon-optimized, RNAi-resistant version of the wild-type gene to restore normal function (Benitec Biopharma). Current clinical candidates, such as BB-301, utilize adeno-associated virus (AAV) vectors to deliver these components directly to affected muscles (ClinicalTrials.gov NCT06348472).

Other names

PABP2 mRNAPABP-2 mRNAPAB1 mRNAPoly(A) binding protein 2 mRNAPoly(A) binding protein nuclear 1 mRNA

RNA interference-mediated knockdown of endogenous PABPN1 mRNA combined with gene replacement of RNAi-resistant wild-type PABPN1.