Listening to silence and understanding nonsense: exonic mutations that affect splicing
Abstract
Point mutations in the coding regions of genes are commonly assumed to exert their effects by altering single amino acids in the encoded proteins. However, there is increasing evidence that many human disease genes harbour exonic mutations that affect pre-mRNA splicing. Nonsense, missense and even translationally silent mutations can inactivate genes by inducing the splicing machinery to skip the mutant exons. Similarly, coding-region single-nucleotide polymorphisms might cause phenotypic variability by influencing splicing accuracy or efficiency. As the splicing mechanisms that depend on exonic signals are elucidated, new therapeutic approaches to treating certain genetic diseases can begin to be explored.
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Human disease mutations often disrupt cis-elements that control splicing and result in aberrant alternative splicing patterns.
“Human disease mutations often disrupt cis-elements that control splicing and result in aberrant AS patterns (Cartegni et al., 2002).”
From A Highly Conserved Program of Neuronal Microexons Is Misregulated in Autistic Brains (2014) · cites this paper as Cartegni et al., 2002
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- Authors
- Cartegni, L., Chew, S. L., & Krainer, A. R.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- St Bartholomew's Hospital (GB)
- Corresponding author
- Krainer, Adrian R.
- Venue
- Nature Reviews Genetics
- Published
- 2002-04
- Volume
- 3
- Issue
- 4
- Pages
- 285-298
- ISSN
- 1471-0056 (ISSN-L)
- 1471-0064
- OpenAlex
- W2063318299
- Cited by
- 2,209
- References
- 151
- Citations by year
- 2026: 32 · 2025: 47 · 2024: 49 · 2023: 51 · 2022: 72 · 2021: 65 · 2020: 78 · 2019: 74 · 2018: 66 · 2017: 70 · 2016: 70 · 2015: 72 · 2014: 96 · 2013: 105 · 2012: 92
- FWCI
- 10.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Genetics (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- exonic mutations, pre-mRNA splicing, nonsense mutation, missense mutations, exon skipping, single nucleotide polymorphisms, splicing errors, genetic disorders, splicing-targeted therapy, phenotypic variability
- MeSH terms
- Enhancer Elements, Genetic, Exons, Humans, Nuclear Proteins, Phenotype, RNA Splicing, RNA, Messenger, Open Reading Frames, Point Mutation, Codon, Nonsense, Mutation, Missense
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