Poly(A) binding protein nuclear 1 (PABPN1)

Poly(A) binding protein nuclear 1 (PABPN1) is a nuclear protein essential for the efficient polyadenylation of messenger RNA (mRNA) precursors. It binds to the poly(A) tail of mRNA, stimulating poly(A) polymerase and regulating the length of the tail, which is critical for mRNA stability and nuclear export (UniProt Q86U42). Mutations in the PABPN1 gene, specifically an expansion of the GCG trinucleotide repeat, result in Oculopharyngeal Muscular Dystrophy (OPMD), a progressive muscle-wasting disease (NIH GARD). The mutant protein forms toxic intranuclear inclusions that disrupt cellular homeostasis and lead to muscle fiber atrophy. Therapeutic strategies like BB-301 utilize a silence and replace approach, where a codon-optimized PABPN1 transgene is delivered to restore wild-type protein function while endogenous mutant PABPN1 is suppressed via RNA interference (Benitec Biopharma). The codon optimization allows the transgene to escape silencing by the co-delivered shRNAs, providing a functional replacement for the defective protein while minimizing the risk of aggregation (PMID: 28813530).

Other names

PABP2PABP-2Polyadenylate-binding protein 2OPMDCodon-optimized PABPN1

Gene replacement and suppression (silence and replace strategy)