ArticleProceedings of the National Academy of Sciences of the United States of America2005
Sequence conservation, relative isoform frequencies, and nonsense-mediated decay in evolutionarily conserved alternative splicing.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed.
- An in vivo parallelized reporter assay to uncover tissue-specific splicing regulatory sequences in a multicellular animal.Nucleic acids research · 2026Article
- Quest for Orthologs in the era of Data Deluge and AI: Challenges and Innovations in Orthology Prediction and Data Integration.Journal of molecular evolution · 2025Review
- SpliceDecoder: A High-Throughput Tool for Guiding the Functional Interpretation of Differential Splicing Events.bioRxiv : the preprint server for biology · 2025Article
- Coordinated expression of retained introns and poison exons in renal cell carcinoma.Cell reports · 2025Article
- Ubiquitous conservative interaction patterns between post-spliced introns and their mRNAs revealed by genome-wide interspecies comparison.Frontiers in genetics · 2023Article
- Inefficient splicing of long non-coding RNAs is associated with higher transcript complexity in human and mouse.RNA biology · 2023Article
- FOXA1 regulates alternative splicing in prostate cancer.Cell reports · 2022Article
- The endogenous HBZ interactome in ATL leukemic cells reveals an unprecedented complexity of host interacting partners involved in RNA splicing.Frontiers in immunology · 2022Article
- Article
- Expression and clinical importance of a newly discovered alternative splice variant of the gene for acrosin binding protein found in human brain tumors.Asian biomedicine : research, reviews and news · 2020Article
- Dynamic changes in intron retention are tightly associated with regulation of splicing factors and proliferative activity during B-cell development.Nucleic acids research · 2020Article
- Effect of expression alteration in flanking genes on phenotypes of St8sia2-deficient mice.Scientific reports · 2019Article
- Identification of genes underlying phenotypic plasticity of wing size via insulin signaling pathway by network-based analysis in Sogatella furcifera.BMC genomics · 2019Article
- Origin of exon skipping-rich transcriptomes in animals driven by evolution of gene architecture.Genome biology · 2018Article
- Unexpected conservation of the RNA splicing apparatus in the highly streamlined genome of Galdieria sulphuraria.BMC evolutionary biology · 2018Article
- The PRMT5/WDR77 complex regulates alternative splicing through ZNF326 in breast cancer.Nucleic acids research · 2017Article
- Transcriptome analysis of hypoxic cancer cells uncovers intron retention in EIF2B5 as a mechanism to inhibit translation.PLoS biology · 2017Article
- An Ultraconserved Element (UCE) controls homeostatic splicing of ARGLU1 mRNA.Nucleic acids research · 2017Article
- Correspondence of D. melanogaster and C. elegans developmental stages revealed by alternative splicing characteristics of conserved exons.BMC genomics · 2017Article
- IRFinder: assessing the impact of intron retention on mammalian gene expression.Genome biology · 2017Article
17 more citing papers are in PubMed but not listed here.
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2 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Studies of expressed sequence tag data sets have revealed large numbers of splicing variants for human genes, but it remains challenging to distinguish functionally important variants from aberrant splicing, clarify the nature of the alternative functions, and understand the signals that regulate splicing choices. To help address these issues, we have constructed and analyzed a large data set of 1,478 exon-skipping alternative splicing (AS) variants evolutionarily conserved in human and mouse. In about one-fifth of cases, one isoform appears subject to nonsense-mediated mRNA decay (NMD), supporting the idea that a major role of AS is to regulate gene expression; one-quarter of these NMD-inducing cases involve a conserved exon whose apparent sole purpose is to mediate destruction of the message when included. We explore sequence conservation likely related to splicing regulation, using in part a measure of the overall amount of conserved information in a sequence, and find that the increased conservation that has been observed within AS exons primarily affects synonymous sites, suggesting that regulatory signals significantly constrain synonymous substitution rates. We show that a lower frequency of the inclusion isoform relative to the exclusion isoform tends to be associated with weaker splice site signals, smaller exon size, and higher intronic sequence conservation, and provide evidence that all of these factors are under selection to control relative isoform frequencies. Some conserved instances of AS appear to represent aberrant splicing events that by chance have occurred in both species, and we develop a nonparametric likelihood approach to identify these.
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