RNA-sequencing: A powerful tool for investigating gene expression in amyotrophic lateral sclerosis (ALS)

✍️ Author: Dr Eleni Christoforidou

🕒 Approximate reading time: 4 minutes

RNA-sequencing (RNA-seq) is a high-throughput sequencing technology that allows researchers to study the transcriptome – the complete set of RNA transcripts produced by the genome – in a given sample. By providing a comprehensive view of gene expression, RNA-seq has become a valuable tool for investigating the molecular mechanisms underlying various diseases, including amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterised by the progressive loss of motor neurons in the brain and spinal cord.

The Power of RNA-sequencing

RNA-seq offers several advantages over traditional methods of gene expression analysis, such as microarrays:

1. High sensitivity and specificity: RNA-seq can detect both lowly and highly expressed transcripts, as well as discriminate between closely related genes and isoforms.

2. Unbiased analysis: Unlike microarrays, RNA-seq does not rely on predetermined probes, allowing for the unbiased discovery of novel transcripts, isoforms, and fusion genes.

3. Quantitative accuracy: RNA-seq provides precise quantification of gene expression levels, enabling the detection of subtle changes in transcript abundance. RNA-sequencing in ALS Research

RNA-seq has been widely employed in ALS research, providing valuable insights into the disease's molecular mechanisms and identifying potential therapeutic targets:

1. Differential gene expression: RNA-seq has been used to identify genes and pathways that are differentially expressed in ALS patients compared to healthy controls, shedding light on the processes that drive motor neuron degeneration.

2. Alternative splicing: RNA-seq has revealed widespread alterations in alternative splicing – the process by which different mRNA isoforms are generated from the same gene – in ALS, highlighting its potential role in disease pathogenesis.

3. Non-coding RNA expression: RNA-seq has facilitated the discovery of novel non-coding RNAs, such as microRNAs and long non-coding RNAs, that may contribute to ALS pathology by regulating gene expression.

Therapeutic Implications

By providing a comprehensive view of the ALS transcriptome, RNA-seq has the potential to identify novel therapeutic targets and inform the development of more effective treatments for the disease:

1. Targeting dysregulated genes and pathways: The identification of differentially expressed genes in ALS can inform the development of therapies aimed at modulating the activity of these genes or their associated pathways.

2. Splicing modulators: The discovery of widespread alterations in alternative splicing in ALS raises the possibility of using splicing modulators to correct these abnormalities and ameliorate motor neuron dysfunction.

3. Non-coding RNA-based therapies: The identification of dysregulated non-coding RNAs in ALS opens up new avenues for therapeutic intervention, such as using antisense oligonucleotides or small molecules to modulate their expression or function.

Conclusion

RNA-sequencing has emerged as a powerful tool for investigating gene expression in amyotrophic lateral sclerosis (ALS), providing valuable insights into the disease's molecular mechanisms and identifying potential therapeutic targets. Continued research employing RNA-seq and other high-throughput technologies will be crucial for advancing our understanding of ALS and developing novel treatments to slow or halt the progression of this devastating neurodegenerative disease.