ArticleGenome biology2007
Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns.
Article in Genome biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- A-Z of Epigenetic Readers: Targeting Alternative Splicing and Histone Modification Variants in Cancer.Cancers · 2024Review
- Global analysis of binding sites of U2AF1 and ZRSR2 reveals RNA elements required for mutually exclusive splicing by the U2- and U12-type spliceosome.Nucleic acids research · 2024Article
- Nucleotides in both donor and acceptor splice sites are responsible for choice in NAGNAG tandem splice sites.Cellular and molecular life sciences : CMLS · 2021Article
- Comprehensive database and evolutionary dynamics of U12-type introns.Nucleic acids research · 2020Article
- Functionally Overlapping Variants Control Tuberculosis Susceptibility in Collaborative Cross Mice.mBio · 2019Article
- PUF60-activated exons uncover altered 3' splice-site selection by germline missense mutations in a single RRM.Nucleic acids research · 2018Article
- Characterisation of Antigen B Protein Species Present in the Hydatid Cyst Fluid of Echinococcus canadensis G7 Genotype.PLoS neglected tropical diseases · 2017Article
- Splice Sites Seldom Slide: Intron Evolution in Oomycetes.Genome biology and evolution · 2016Article
- Gene Model Annotations for Drosophila melanogaster: The Rule-Benders.G3 (Bethesda, Md.) · 2015Article
- Article
- Physiological state co-regulates thousands of mammalian mRNA splicing events at tandem splice sites and alternative exons.Nucleic acids research · 2014Article
- A comprehensive survey of non-canonical splice sites in the human transcriptome.Nucleic acids research · 2014Article
- The complex intron landscape and massive intron invasion in a picoeukaryote provides insights into intron evolution.Genome biology and evolution · 2013Article
- Article
- A novel ARMS2 splice variant is identified in human retina.Experimental eye research · 2012Article
- Constant splice-isoform ratios in human lymphoblastoid cells support the concept of a splico-stat.Genetics · 2011Article
- TassDB2 - A comprehensive database of subtle alternative splicing events.BMC bioinformatics · 2010Article
- Analysis of splicing patterns by pyrosequencing.Nucleic acids research · 2009Article
- Accurate prediction of NAGNAG alternative splicing.Nucleic acids research · 2009Article
- Selection against tandem splice sites affecting structured protein regions.BMC evolutionary biology · 2008Article
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite some degeneracy of sequence signals that govern splicing of eukaryotic pre-mRNAs, it is an accepted rule that U2-dependent introns exhibit the 3' terminal dinucleotide AG. Intrigued by anecdotal evidence for functional non-AG 3' splice sites, we carried out a human genome-wide screen.
resultsWe identified TG dinucleotides functioning as alternative 3' splice sites in 36 human genes. The TG-derived splice variants were experimentally validated with a success rate of 92%. Interestingly, ratios of alternative splice variants are tissue-specific for several introns. TG splice sites and their flanking intron sequences are substantially conserved between orthologous vertebrate genes, even between human and frog, indicating functional relevance. Remarkably, TG splice sites are exclusively found as alternative 3' splice sites, never as the sole 3' splice site for an intron, and we observed a distance constraint for TG-AG splice site tandems.
conclusionSince TGs splice sites are exclusively found as alternative 3' splice sites, the U2 spliceosome apparently accomplishes perfect specificity for 3' AGs at an early splicing step, but may choose 3' TGs during later steps. Given the tiny fraction of TG 3' splice sites compared to the vast amount of non-viable TGs, cis-acting sequence signals must significantly contribute to splice site definition. Thus, we consider TG-AG 3' splice site tandems as promising subjects for studies on the mechanisms of 3' splice site selection.
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