Abstract
BackgroundSome mutations in the internal regions of exons occur within splicing enhancers and silencers, influencing the pattern of alternative splicing in the corresponding genes. To understand how these sequence changes affect splicing, we created a database of these mutations.FindingsThe Alternative Splicing Mutation Database (ASMD) serves as a repository for all exonic mutations not associated with splicing junctions that measurably change the pattern of alternative splicing. In this initial published release (version 1.2), only human sequences are present, but the ASMD will grow to include other organisms, (see Availability and requirements section for the ASMD web address).This relational database allows users to investigate connections between mutations and features of the surrounding sequences, including flanking sequences, RNA secondary structures and strengths of splice junctions. Splicing effects of the mutations are quantified by the relative presence of alternative mRNA isoforms with and without a given mutation. This measure is further categorized by the accuracy of the experimental methods employed. The database currently contains 170 mutations in 66 exons, yet these numbers increase regularly.We developed an algorithm to derive a table of oligonucleotide Splicing Potential (SP) values from the ASMD dataset. We present the SP concept and tools in detail in our corresponding article.ConclusionThe current data set demonstrates that mutations affecting splicing are located throughout exons and might be enriched within local RNA secondary structures. Exons from the ASMD have below average splicing junction strength scores, but the difference is small and is judged not to be significant.
Highlights
Some mutations in the internal regions of exons occur within splicing enhancers and silencers, influencing the pattern of alternative splicing in the corresponding genes
The current data set demonstrates that mutations affecting splicing are located throughout exons and might be enriched within local RNA secondary structures
Exons from the Alternative Splicing Mutation Database (ASMD) have below average splicing junction strength scores, but the difference is small and is judged not to be significant
Summary
Some mutations in the internal regions of exons occur within splicing enhancers and silencers, influencing the pattern of alternative splicing in the corresponding genes. The regulation of alternative splicing is a very intricate process which involves the interaction of dozens of spliceosomal proteins with a great variety of short sequence motifs inside exons and introns These regulatory motifs are known as exonic splicing enhancers (ESEs), exonic splicing silencers (ESSs), intronic splicing enhancers (ISEs), and intronic splicing silencers (ISSs) [1,3]. Significant progress in understanding AS has been achieved in experimental research that characterized a number of splicing enhancers and silencers [5,6,7,8,9] and in several bioinformatics approaches for computational inference of ESEs and ESSs [10,11,12,13,14,15,16,17,18] Despite this progress, one cannot predict a tendency to alternative splicing from genomic data. A set of mutations known to be associated with alternative splicing effects (reviewed by [19,9]) provides valuable raw material for a broad range of studies aiming to elucidate mechanisms of spliceosomal regulation
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