Predictive Identification of Exonic Splicing Enhancers in Human Genes

@article{Fairbrother2002PredictiveIO,
  title={Predictive Identification of Exonic Splicing Enhancers in Human Genes},
  author={William G. Fairbrother and Rufang Yeh and Phillip A. Sharp and Christopher B. Burge},
  journal={Science},
  year={2002},
  volume={297},
  pages={1007 - 1013}
}
Specific short oligonucleotide sequences that enhance pre-mRNA splicing when present in exons, termed exonic splicing enhancers (ESEs), play important roles in constitutive and alternative splicing. A computational method, RESCUE-ESE, was developed that predicts which sequences have ESE activity by statistical analysis of exon-intron and splice site composition. When large data sets of human gene sequences were used, this method identified 10 predicted ESE motifs. Representatives of all 10… 
Distribution of exonic splicing enhancer elements in human genes.
TLDR
ESEs are enriched in regions in exons that are close to the splice sites, especially in the region 80 to 120 bases away from the ends of splice acceptor sites, which may help to predict functional ESE sites in RNA sequences.
Over-representation of exonic splicing enhancers in human intronless genes suggests multiple functions in mRNA processing.
TLDR
There is evidence that intronless transcripts display a significantly higher frequency of both shuttling and non-shuttling SR protein binding sites compared to intron-containing sequences, suggesting that SR proteins play a role in cellular processes distinct from splicing.
Analysis of mutations that influence pre-mRNA splicing.
TLDR
A recombination-based system that allows for the generation of splicing reporter constructs in the first week and their subsequent analysis in the second week, and a bioinformatic analysis that determines the influence of a mutation on splicing enhancers and silencers, splice sites and RNA secondary structures.
Systematic Identification and Analysis of Exonic Splicing Silencers
TLDR
ExonScan and related bioinformatic analyses suggest that these ESS motifs play important roles in suppression of pseudoexons, in splice site definition, and in AS.
Evolutionarily Conserved Intronic Splicing Regulatory Elements in the Human Genome
TLDR
This work has shown that intronic splicing elements that are evolutionarily conserved across multiple species play important roles in the regulation of constitutive splicing, where a single mRNA is produced, and alternative splice, where multiple mRNA isoforms are generated.
Identification of a splicing enhancer in MLH1 using COMPARE, a new assay for determination of relative RNA splicing efficiencies.
TLDR
A flexible in vitro method is described that can be used to functionally compare the effects of multiple sequence variants on ESE activity in a single in vitro splicing reaction and shows that sequences from this exon can replace an ESE from the mouse IgM gene to support RNA splicing in HeLa nuclear extracts.
A Machine Learning Strategy to Identity Exonic Splice Enhancers in Human Protein-coding Sequence
TLDR
A novel strategy for analysing protein-coding sequence by first randomizing the codons used at each position within the coding sequence, then applying a motif-based machine learning algorithm to compare the true and randomized sequences succeeded in detecting signals in coding exons which seem to be orthogonal to the sequences' primary function of coding for proteins.
Systematic characterization of short intronic splicing-regulatory elements
TLDR
A complete pentamer-sequence library that comprises all possible combinations of 5 nucleotides in intron 7, at a fixed site downstream of the 5′ splice site is generated, providing a valuable resource for understanding how short RNA sequences regulate splicing.
Exonic splicing enhancers and exonic splicing silencers
TLDR
A variety of methods, both experimental and computational, have been used to identify functional ESEs and ESSs; mutations in these splicing signals are increasingly recognized as responsible for human genetic disease.
Genomic features defining exonic variants that modulate splicing
TLDR
A number of features that have statistically significant representation among exonic variants that modulate splicing are identified, highlighting putative mechanisms responsible for splicing outcome and emphasize the role of features important for exon definition.
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TLDR
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