ArticleBMC biology2009
Noisy splicing, more than expression regulation, explains why some exons are subject to nonsense-mediated mRNA decay.
Article in BMC biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 78 citations in OpenAlex.
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- Splicing accuracy varies across human introns, tissues, age and disease.Nature communications · 2025Article
- Exome sequencing reveals neurodevelopmental genes in simplex consanguineous Iranian families with syndromic autism.BMC medical genomics · 2024Article
- Unraveling the Concealed Transcriptomic Landscape of PTEN in Human Malignancies.Current genomics · 2023Article
- Extending and outlining the genotypic and phenotypic spectrum of novel mutations of NALCN gene in IHPRF1 syndrome: identifying recurrent urinary tract infection.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Article
- Variants in EFCAB7 underlie nonsyndromic postaxial polydactyly.European journal of human genetics : EJHG · 2023Article
- Detailed analysis of an enriched deep intronic ABCA4 variant in Irish Stargardt disease patients.Scientific reports · 2023Article
- Effective splicing restoration of a deep-intronicMolecular therapy. Nucleic acids · 2022Article
- Identification of a novel de novo mutation in the CTNNB1 gene in an Iranian patient with intellectual disability.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Article
- In rice splice variants that restore the reading frame after frameshifting indel introduction are common, often induced by the indels and sometimes lead to organism-level rescue.PLoS genetics · 2022Article
- Platinum-based chemotherapy for pancreatic cancer: impact of mutations in the homologous recombination repair and Fanconi anemia genes.Therapeutic advances in medical oncology · 2022Article
- Hyper-IgE Syndrome due to an Elusive Novel Intronic Homozygous Variant in DOCK8.Journal of clinical immunology · 2022Article
- Evidence for the Association between the Intronic Haplotypes of Ionotropic Glutamate Receptors and First-Episode Schizophrenia.Journal of personalized medicine · 2021Article
- Single-molecule, full-length transcript isoform sequencing reveals disease-associated RNA isoforms in cardiomyocytes.Nature communications · 2021Article
- A Novel Non-Coding Variant in DCLRE1C Results in Deregulated Splicing and Induces SCID Through the Generation of a Truncated ARTEMIS Protein That Fails to Support V(D)J Recombination and DNA Damage Repair.Frontiers in immunology · 2021Article
- Detailed Phenotyping and Therapeutic Strategies for Intronic ABCA4 Variants in Stargardt Disease.Molecular therapy. Nucleic acids · 2020Article
- tappAS: a comprehensive computational framework for the analysis of the functional impact of differential splicing.Genome biology · 2020Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNonsense-mediated decay is a mechanism that degrades mRNAs with a premature termination codon. That some exons have premature termination codons at fixation is paradoxical: why make a transcript if it is only to be destroyed? One model supposes that splicing is inherently noisy and spurious transcripts are common. The evolution of a premature termination codon in a regularly made unwanted transcript can be a means to prevent costly translation. Alternatively, nonsense-mediated decay can be regulated under certain conditions so the presence of a premature termination codon can be a means to up-regulate transcripts needed when nonsense-mediated decay is suppressed.
resultsTo resolve this issue we examined the properties of putative nonsense-mediated decay targets in humans and mice. We started with a well-annotated set of protein coding genes and found that 2 to 4% of genes are probably subject to nonsense-mediated decay, and that the premature termination codon reflects neither rare mutations nor sequencing artefacts. Several lines of evidence suggested that the noisy splicing model has considerable relevance: 1) exons that are uniquely found in nonsense-mediated decay transcripts (nonsense-mediated decay-specific exons) tend to be newly created; 2) have low-inclusion level; 3) tend not to be a multiple of three long; 4) belong to genes with multiple splice isoforms more often than expected; and 5) these genes are not obviously enriched for any functional class nor conserved as nonsense-mediated decay candidates in other species. However, nonsense-mediated decay-specific exons for which distant orthologous exons can be found tend to have been under purifying selection, consistent with the regulation model.
conclusionWe conclude that for recently evolved exons the noisy splicing model is the better explanation of their properties, while for ancient exons the nonsense-mediated decay regulated gene expression is a viable explanation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.