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Published on: August 15, 2019
RNA-dominant diseases
Robert J Osborne1, Charles A Thornton
1Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Abstract:
Several examples have come to light in which mutations in non-protein-coding regions give rise to a deleterious gain-of-function by non-coding RNA. Expression of the toxic RNA is associated with formation of nuclear inclusions and late-onset degenerative changes in brain, heart or skeletal muscle. In the best studied example, myotonic dystrophy, it appears that the main pathogenic effect of the toxic RNA is to sequester binding proteins and compromise the regulation of alternative splicing. This review describes some of the recent advances in understanding the pathophysiology of RNA-dominant diseases.
Insights
Mutations in non-protein-coding regions can cause toxic non-coding RNA, leading to degenerative diseases. This RNA interferes with protein binding and alternative splicing regulation.
Area of Science:
- Molecular Biology
- Genetics
- Neuroscience
Background:
- Mutations in non-protein-coding regions are increasingly recognized as disease-causing.
- Non-coding RNA can exert toxic gain-of-function effects.
- These effects are linked to nuclear inclusions and late-onset neurodegenerative and myodegenerative disorders.
Purpose of the Study:
- To review recent advances in understanding the pathophysiology of RNA-dominant diseases.
- To highlight the role of toxic non-coding RNA in disease.
- To discuss the mechanisms by which toxic RNA causes cellular dysfunction.
Main Methods:
- Literature review of studies on RNA-dominant diseases.
- Analysis of molecular mechanisms underlying toxic RNA function.
- Case studies, focusing on myotonic dystrophy as a model.
Main Results:
- Toxic non-coding RNA expression correlates with nuclear inclusions and tissue degeneration.
- In myotonic dystrophy, toxic RNA sequesters RNA-binding proteins.
- Compromised regulation of alternative splicing is a key pathogenic mechanism.
Conclusions:
- RNA-dominant diseases represent a significant class of genetic disorders.
- Understanding the pathophysiology of toxic RNA is crucial for developing therapeutic strategies.
- Further research into non-coding RNA function and dysfunction is warranted.
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