AAT Bioquest

Are spliceosomes associated with any diseases?

Posted March 14, 2024


Research suggests that errors in the splicing process play a significant role in the development and progression of various diseases including cancer, muscular dystrophies, and neurodegenerative diseases. When the splicing process isn't tightly controlled, it can lead to these mis-splicing events. A significant number of human diseases result from either the dysregulation of the entire spliceosome or incorrect splicing of a single gene. Approximately 35% of genetic disorders in humans stem from mutations that disrupt the splicing of a single gene. These mutations can alter splice sites (e.g. via deletion or addition) leading to conditions like α- or β-thalassemia. They can also impact alternative splicing, affecting the inclusion or exclusion of specific exons (e.g. as seen in frontotemporal dementia caused by tau mis-splicing). Additionally, mutations in spliceosomal proteins (such as Prp8,Prp31,Brr2, and Prp3) can cause conditions like autosomal dominant retinitis pigmentosa. Mutations in splicing factors like U2AF35 and SF3B1 are commonly associated with chronic lymphocytic leukemia and myelodysplasia. Misregulation of splicing factor levels is associated with other cancers as well. Some splicing errors produce mRNA isoforms that are quickly degraded, leading to significant changes in abundance and protein structure due to single point mutations. 

Additional resources

Spliceosomopathies: Diseases and mechanisms

DNA and RNA Quantitation

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