Transcriptome sequencing reveals aberrant alternative splicing in Huntington's disease

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Huntington's disease (HD) is a neurodegenerative disorder caused by genetic mutations.
• Transcriptome dysregulation is a known feature of HD pathogenesis.
• Previous studies focused on gene expression, neglecting post-transcriptional changes like alternative splicing.

Purpose of the Study:

• To systematically discover aberrant alternative splicing events in HD.
• To characterize potential associated splicing factors in HD.
• To investigate the role of alternative splicing in HD pathogenesis.

Main Methods:

• Deep RNA-sequencing (RNA-seq) analysis of motor cortex (BA4) from human HD brains and controls.
• Identification and validation of differential alternative splicing events.
• Analysis of splicing factor expression levels in patient tissues.

Main Results:

• Identified 593 differential alternative splicing events between HD and control brains.
• Discovered four splicing factors with significantly altered expression in HD brains.
• Demonstrated the impact of splicing factor PTBP1 on disease-associated splicing patterns.

Conclusions:

• Provided genomic evidence for widespread splicing dysregulation in HD brains.
• Suggested a significant role for aberrant alternative splicing in HD pathogenesis.
• Highlighted PTBP1 as a key splicing factor in HD progression.