ArticlePloS one2012
Evolutionary constraint helps unmask a splicing regulatory region in BRCA1 exon 11.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Alternative Splicing in Cyclin-Dependent Kinase 4/6 Inhibitor Resistance in Estrogen Receptor-Positive Breast Cancer.Drug development research · 2026Review
- Biallelic GermlineInternational journal of molecular sciences · 2024Article
- Functional Characterization of the Human BRCA1 ∆11 Splicing Isoforms in Yeast.International journal of molecular sciences · 2024Article
- Assessing the Impact of NovelCells · 2024Article
- Aberrant alternative splicing in breast cancer.Journal of molecular cell biology · 2019Review
- BRCA1-No Matter How You Splice It.Cancer research · 2019Review
- Mechanism for survival of homozygous nonsense mutations in the tumor suppressor geneProceedings of the National Academy of Sciences of the United States of America · 2018Article
- A study of splicing mutations in disorders of sex development.Scientific reports · 2017Article
- Combined genetic and splicing analysis of BRCA1 c.[594-2A>C; 641A>G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms.Human molecular genetics · 2016Article
- BRCA1 EXON 11, a CERES (composite regulatory element of splicing) element involved in splice regulation.International journal of molecular sciences · 2014Article
- BRCA1 exon 11 a model of long exon splicing regulation.RNA biology · 2014Article
- Article
- SpliceAid-F: a database of human splicing factors and their RNA-binding sites.Nucleic acids research · 2013Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlternative splicing across exon 11 produces several BRCA1 isoforms. Their proportion varies during the cell cycle, between tissues and in cancer suggesting functional importance of BRCA1 splicing regulation around this exon. Although the regulatory elements driving exon 11 splicing have never been identified, a selective constraint against synonymous substitutions (silent nucleotide variations that do not alter the amino acid residue sequence) in a critical region of BRCA1 exon 11 has been reported to be associated with the necessity to maintain regulatory sequences. METHODOLOGY/PRINCIPAL
findingsHere we have designed a specific minigene to investigate the possibility that this bias in synonymous codon usage reflects the need to preserve the BRCA1 alternative splicing program. We report that in-frame deletions and translationally silent nucleotide substitutions in the critical region affect splicing regulation of BRCA1 exon 11. CONCLUSIONS/SIGNIFICANCE: Using a hybrid minigene approach, we have experimentally validated the hypothesis that the need to maintain correct alternative splicing is a selective pressure against translationally silent sequence variations in the critical region of BRCA1 exon 11. Identification of the trans-acting factors involved in regulating exon 11 alternative splicing will be important in understanding BRCA1-associated tumorigenesis.
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