Mutant Ataxin-7 messenger RNA (mutant ATXN7 mRNA) (mutant ATXN7 mRNA)

Mutant ATXN7 mRNA is the transcript of the Ataxin-7 gene containing an expanded CAG repeat sequence, which translates into a toxic polyglutamine (polyQ) tract in the resulting protein [1]. This mutation is the underlying cause of Spinocerebellar Ataxia Type 7 (SCA7), a rare autosomal dominant neurodegenerative disease characterized by progressive ataxia and cone-rod retinal dystrophy [4]. The mutant mRNA serves as a critical therapeutic target because its degradation prevents the synthesis of the mutant Ataxin-7 protein, which otherwise aggregates and disrupts cellular processes, particularly within the SAGA (Spt-Ada-Gcn5 acetyltransferase) transcription mutant complex [1, 2]. Current drug development efforts focus on using antisense oligonucleotides (ASOs) or RNA interference (RNAi) to selectively bind and degrade the mutant transcript [2, 3]. A major challenge in targeting this molecule is achieving allele-specific knockdown to preserve the expression of the wild-type ATXN7 mRNA, which is essential for normal transcriptional regulation [3]. Successful reduction of mutant ATXN7 mRNA levels has shown promise in preclinical models for halting disease progression and improving motor and visual functions [2]. Therapeutic interventions are typically delivered via intrathecal injection to reach the central nervous system or intravitreal injection for retinal targeting [3, 4].

Other names

SCA7 mRNAAtaxin-7 mRNAATXN7 transcriptMutant ATXN7 transcript

RNase H-mediated cleavage of the target mRNA or RNA-induced silencing complex (RISC)-mediated degradation to prevent translation of toxic protein.