2,6-Diaminopurine Induces ACTN3 Premature Termination Codon Readthrough - PubMed
19 hours ago
- #ACTN3 gene
- #translational readthrough
- #muscle genetics
- The ACTN3 gene encodes α-actinin-3, crucial in fast-twitch muscle fibers, with a common R577X nonsense mutation causing a premature termination codon.
- Individuals homozygous for ACTN3 577XX lack α-actinin-3 protein, leading to reduced athletic performance and muscle mass due to nonsense-mediated mRNA decay.
- 2,6-Diaminopurine (DAP) induces translational readthrough of the PTC at low μM concentrations, restoring full-length α-actinin-3 without needing NMD inhibition.
- Full-length α-actinin-3 from ACTN3 577X forms more homodimers than from ACTN3 577R, suggesting potential functional restoration in humans.
- The study highlights DAP as a promising natural compound for therapeutic readthrough, overcoming limitations of high-dose aminoglycosides.