Ataxin-2 messenger RNA (ATXN2 mRNA)

Ataxin-2 messenger RNA (ATXN2 mRNA) is the transcript of the ATXN2 gene, which encodes a protein essential for RNA metabolism, translation regulation, and the formation of stress granules (UniProt P54252). Pathogenic expansions of CAG trinucleotide repeats within the ATXN2 gene result in a polyglutamine-expanded protein that causes Spinocerebellar ataxia type 2 (SCA2) (Scoles et al., 2017, Nature). Furthermore, intermediate-length CAG repeats in the ATXN2 gene have been identified as a significant genetic risk factor for Amyotrophic lateral sclerosis (ALS) (Elden et al., 2010, Nature). As a therapeutic target, ATXN2 mRNA is addressed using antisense oligonucleotides (ASOs) such as BIIB105 (Ionis Pharmaceuticals). These ASOs are designed to bind specifically to the ATXN2 transcript and induce its degradation via RNase H1, thereby reducing the translation of the toxic Ataxin-2 protein. By lowering the levels of pathogenic Ataxin-2, these therapies aim to mitigate the protein aggregation and cellular stress that drive neurodegeneration. This therapeutic strategy is currently being evaluated in clinical trials to assess its safety and potential to slow disease progression in patients with SCA2 and ALS.

Other names

ATXN2 transcriptSCA2 mRNAASL13 mRNAAtaxin-2 mRNA

Antisense oligonucleotide-mediated degradation of mRNA via RNase H1, leading to reduced translation of the Ataxin-2 protein.