Q&A: What role does alternative splicing play in neurodegenerative disease?

Alternative splicing, a clever way a cell generates many different variations of messenger RNAs—single-stranded RNAs involved in protein synthesis—

and proteins from the same stretch of DNA, plays an important role in molecular biology.

Progressing rapidly, the field of alternative splicing is a complex topic and the scientific literature on it is already extensive.

David Nikom, a student in the UC Riverside Neuroscience Graduate Program, and his advisor, Sika Zheng,

an associate professor of biomedical sciences in the UCR School of Medicine and director of the Center for RNA Biology and Medicine,

have written a review in Nature Reviews Neuroscience to discuss emerging research and evidence of the roles of alternative splicing defects in major neurodegenerative diseases.

They also summarize the latest advances in RNA-based therapeutic strategies to target these disorders.

According to them, the topic of alternative splicing in neurodegenerative disease is particularly relevant in view of the increasing frequency of neurodegenerative disease worldwide and

the urgent need for novel approaches for their treatment and management.

They argue that since aberrant splicing dysregulation occurs commonly in neurodegenerative disease,

the promise of using RNA therapies is important to understand and well-suited for a review.

Titled "Alternative Splicing in Neurodegenerative Disease and the Promise of RNA Therapies," their review aims at providing comprehensive,

all-inclusive knowledge for a scientific audience interested in the topic.

It synthesizes knowledge and discoveries from decades of research made by many labs worldwide on Alzheimer's disease,

Parkinson's disease, Huntington's disease, ALS, frontal temporal dementia, etc. In the following Q&A, Zheng and Nikom unpack key aspects of the review.

What is alternative splicing dysregulation? Once the DNA of a gene is transcribed into a pre-messenger RNA (RNA before it is spliced),

only a small fraction of the pre-messenger RNA makes into the final messenger RNA, or mRNA, transcript that encodes protein.

Alternative splicing is a process by which a cell can select which of those protein-coding parts to include in the resulting RNA or protein.

Alternative splicing dysregulation is when this process goes wrong in some way.

The cell chooses to include the wrong protein-coding parts or exclude some correct parts.

This can cause all sorts of problems with the resulting protein: it could be shorter than it is supposed to be which would disrupt its normal function in the cell,

or it could result in the protein not being produced at all.


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