Cited by 2,209RNA Research and SplicingRNA regulation and diseaseGenomics and Rare Diseases

Listening to silence and understanding nonsense: exonic mutations that affect splicing

Cartegni, Luca, Chew, Shern L., Krainer, Adrian R.·2002·Nature Reviews Genetics

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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Crossref · 10.1038/nrg775

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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
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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