Atrophin-1 pre-messenger RNA (ATN1 pre-mRNA) (ATN1 pre-mRNA)

Atrophin-1 (ATN1) pre-messenger RNA is the primary transcript of the ATN1 gene, which encodes a protein widely expressed in the brain and other tissues [1, 2]. In Dentatorubral-pallidoluysian atrophy (DRPLA), a rare neurodegenerative disorder, a CAG trinucleotide repeat expansion occurs within the ATN1 gene, leading to an elongated polyglutamine tract in the resulting atrophin-1 protein [4]. This mutant protein acquires a toxic gain-of-function, causing neuronal death in the cerebellum and basal ganglia [4]. Therapeutic approaches targeting ATN1 pre-mRNA, such as the antisense oligonucleotide VO659, aim to selectively or preferentially reduce the levels of the expanded transcript [3]. By decreasing the production of the toxic polyglutamine-expanded protein, these therapies intend to slow the progression of ataxia, choreoathetosis, and dementia associated with DRPLA [3, 4].

Other names

Atrophin-1 pre-mRNAATN1 transcriptDRPLA gene transcriptAtrophin-1 precursor mRNA

Antisense oligonucleotide-mediated reduction of mutant transcript levels through RNase H-mediated degradation or steric hindrance of translation [3].