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Updated: Jun 8, 2026
08:35
Identification of Alternative Splicing and Polyadenylation in RNA-seq Data
Published on: June 24, 2021
Alternative splicing at a NAGNAG acceptor site as a novel phenotype modifier
Alexandre Hinzpeter1, Abdel Aissat, Elvira Sondo
1INSERM, Unité U955, Créteil, France.
Plos Genetics
|October 16, 2010
Summary
Alternative splicing at NAGNAG sites can remove disease-causing stop codons, leading to milder cystic fibrosis. This discovery offers new insights for genetic counseling and therapeutic strategies.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Premature termination codons (PTCs) often cause severe genetic disorders.
- Bypassing stop codons can result in milder disease phenotypes.
- Alternative splicing at NAGNAG tandem splice sites can lead to three-nucleotide indels.
Purpose of the Study:
- To investigate the molecular mechanism behind the mild phenotype in cystic fibrosis patients with the E831X mutation.
- To provide experimental evidence for stop codon indel by alternative splicing at NAGNAG sites.
Main Methods:
- Analysis of nasal epithelial cell mRNA to detect isoforms.
- Structure-function studies.
- In silico analyses.
Main Results:
- Identified alternative splicing at a NAGNAG acceptor site causing a stop codon indel.
- Detected three distinct mRNA isoforms in cystic fibrosis patients homozygous for the E831X mutation.
- Provided the first experimental evidence for this specific splicing mechanism.
Conclusions:
- Alternative splicing at NAGNAG tandem sites can remove disease-causing stop codons, contributing to proteome plasticity.
- This mechanism explains the mild to asymptomatic phenotype in certain cystic fibrosis patients.
- Findings are crucial for genetic counseling and developing therapeutic strategies for genetic disorders.
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