New alternative splicing variants of the ATXN2 transcript

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder caused by polyglutamine expansion in ataxin-2.
• Ataxin-2 functions in mRNA translation and endocytosis are not fully understood.
• Previously identified human splice variants of ataxin-2 include those lacking exons 10 and 21.

Purpose of the Study:

• To characterize novel splice variants of ataxin-2.
• To investigate if polyglutamine expansion affects ataxin-2 splicing in spinocerebellar ataxia type 2 (SCA2).

Main Methods:

• Quantitative immunoblots and reverse-transcriptase polymerase-chain-reaction (RT-PCR) were used.
• Sequencing validated the identified splice variants.
• Analysis was performed on human cell lines, mouse, and human brain tissue.

Main Results:

• Novel ataxin-2 splice variants lacking exon 12 and exon 24 were identified.
• These variants were found in human cell lines, mouse, and human brain.
• Splicing of ataxin-2 was not abolished by polyglutamine expansion in SCA2 patient fibroblasts.

Conclusions:

• Ataxin-2 splice isoforms may be relevant for monitoring RNA processing in neurodegenerative diseases.
• Understanding ataxin-2 splicing is important given its interaction with TDP-43 and modulation of ALS risk.
• Further research into ataxin-2 splice variants could inform neuroprotective therapies.