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Exon

About: Exon is a research topic. Over the lifetime, 38308 publications have been published within this topic receiving 1745408 citations. The topic is also known as: exons.


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Journal ArticleDOI
TL;DR: MATS (multivariate analysis of transcript splicing), a Bayesian statistical framework for flexible hypothesis testing of differential alternative splicing patterns on RNA-Seq data, is developed and demonstrated that MATS is an effective and flexible approach for detecting differential alternativesplicing from RNA- Seq data.
Abstract: Ultra-deep RNA sequencing has become a powerful approach for genome-wide analysis of pre-mRNA alternative splicing. We develop MATS (multivariate analysis of transcript splicing), a bayesian statistical framework for flexible hypothesis testing of differential alternative splicing patterns on RNA-Seq data. MATS uses a multivariate uniform prior to model the between-sample correlation in exon splicing patterns, and a Markov chain Monte Carlo (MCMC) method coupled with a simulation-based adaptive sampling procedure to calculate the P-value and false discovery rate (FDR) of differential alternative splicing. Importantly, the MATS approach is applicable to almost any type of null hypotheses of interest, providing the flexibility to identify differential alternative splicing events that match a given user-defined pattern. We evaluated the performance of MATS using simulated and real RNA-Seq data sets. In the RNA-Seq analysis of alternative splicing events regulated by the epithelial-specific splicing factor ESRP1, we obtained a high RT-PCR validation rate of 86% for differential exon skipping events with a MATS FDR of <10%. Additionally, over the full list of RT-PCR tested exons, the MATS FDR estimates matched well with the experimental validation rate. Our results demonstrate that MATS is an effective and flexible approach for detecting differential alternative splicing from RNA-Seq data.

339 citations

Journal ArticleDOI
TL;DR: A meta‐analysis of 478 disease‐associated splicing mutations, in 38 different genes, reveals that exon skipping was the preferred phenotype when the immediate vicinity of the affected exon–intron junctions was devoid of alternative splice‐sites, and estimates that some 1.6% of disease‐causing missense substitutions in human genes are likely to affect the mRNA splicing phenotype.
Abstract: Although single base-pair substitutions in splice junctions constitute at least 10% of all mutations causing human inherited disease, the factors that determine their phenotypic consequences at the RNA level remain to be fully elucidated. Employing a neural network for splice-site recognition, we performed a meta-analysis of 478 disease-associated splicing mutations, in 38 different genes, for which detailed laboratory-based mRNA phenotype assessment had been performed. Inspection of the ±50-bp DNA sequence context of the mutations revealed that exon skipping was the preferred phenotype when the immediate vicinity of the affected exon–intron junctions was devoid of alternative splice-sites. By contrast, in the presence of at least one such motif, cryptic splice-site utilization, became more prevalent. This association was, however, confined to donor splice-sites. Outside the obligate dinucleotide, the spatial distribution of pathological mutations was found to differ significantly from that of SNPs. Whereas disease-associated lesions clustered at positions –1 and +3 to +6 for donor sites and –3 for acceptor sites, SNPs were found to be almost evenly distributed over all sequence positions considered. When all putative missense mutations in the vicinity of splice-sites were extracted from the Human Gene Mutation Database for the 38 studied genes, a significantly higher proportion of changes at donor sites (37/152; 24.3%) than at acceptor splice-sites (1/142; 0.7%) was found to reduce the neural network signal emitted by the respective splice-site. Based upon these findings, we estimate that some 1.6% of disease-causing missense substitutions in human genes are likely to affect the mRNA splicing phenotype. Taken together, our results are consistent with correct donor splice-site recognition being a key step in exon recognition. Hum Mutat 28(2), 150–158, 2007. © 2006 Wiley-Liss, Inc.

339 citations

Journal ArticleDOI
TL;DR: The results demonstrate that the spliceosome can leave behind signature proteins at exon-exon junctions, which could influence downstream metabolic events in vivo such as mRNA transport, translation, and nonsense-mediated decay.
Abstract: We provide direct evidence that pre-mRNA splicing alters mRNP protein composition. Using a novel in vitro cross-linking approach, we detected several proteins that associate with mRNA exon–exon junctions only as a consequence of splicing. Immunoprecipitation experiments suggested that these proteins are part of a tight complex around the junction. Two were identified as SRm160, a nuclear matrix-associated splicing coactivator, and hPrp8p, a core component of U5 snRNP and spliceosomes. Glycerol gradient fractionation showed that a subset of these proteins remain associated with mRNA after its release from the spliceosome. These results demonstrate that the spliceosome can leave behind signature proteins at exon–exon junctions. Such proteins could influence downstream metabolic events in vivo such as mRNA transport, translation, and nonsense-mediated decay.

339 citations

Journal ArticleDOI
14 Jan 2005-Cell
TL;DR: This work identifies the essential splicing factor ASF/SF2 as a key component of the program, regulating a restricted set of tissue-specific alternative splicing events during heart remodeling, and identifies CaMKIIdelta as a fundamental splicing regulator in the reprogramming pathway.

338 citations

Journal ArticleDOI
TL;DR: It is reported that the SR proteins SF2/ASF and 9G8 stimulate EDI splicing in vivo and that their effect requires an intact EDI ESE, suggesting that the transcription machinery modulates their recruitment to the ESE.

338 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20231,618
20222,004
2021905
2020908
2019887
2018909