title: Computational analysis of splicing errors and mutations in human transcripts.
abstract: BACKGROUND
  Most retained introns found in human cDNAs generated by high-throughput sequencing projects seem to result from underspliced transcripts, and thus they capture intermediate steps of pre-mRNA splicing. On the other hand, mutations in splice sites cause exon skipping of the respective exon or activation of pre-existing cryptic sites. Both types of events reflect properties of the splicing mechanism.
  
  
  RESULTS
  The retained introns were significantly shorter than constitutive ones, and skipped exons are shorter than exons with cryptic sites. Both donor and acceptor splice sites of retained introns were weaker than splice sites of constitutive introns. The authentic acceptor sites affected by mutations were significantly weaker in exons with activated cryptic sites than in skipped exons. The distance from a mutated splice site to the nearest equivalent site is significantly shorter in cases of activated cryptic sites compared to exon skipping events. The prevalence of retained introns within genes monotonically increased in the 5'-to-3' direction (more retained introns close to the 3'-end), consistent with the model of co-transcriptional splicing. The density of exonic splicing enhancers was higher, and the density of exonic splicing silencers lower in retained introns compared to constitutive ones and in exons with cryptic sites compared to skipped exons.
  
  
  CONCLUSIONS
  Thus the analysis of retained introns in human cDNA, exons skipped due to mutations in splice sites and exons with cryptic sites produced results consistent with the intron definition mechanism of splicing of short introns, co-transcriptional splicing, dependence of splicing efficiency on the splice site strength and the density of candidate exonic splicing enhancers and silencers. These results are consistent with other, recently published analyses.
authors.affiliation: Institute for Information Transmission Problems (the Kharkevich Institute) RAS, Bolshoi Karetny pereulok 19, Moscow, 127994, Russia. kurmangali@mail.ru
authors.forename: Yerbol Z
authors.initials: YZ
authors.lastname: Kurmangaliyev
authors.forename: Mikhail S
authors.initials: MS
authors.lastname: Gelfand
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D019295:Computational Biology / Q000706:statistics & numerical data; D004252:DNA Mutational Analysis; D030561:Databases, Nucleic Acid; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics*; D014644:Genetic Variation; D023281:Genomics; D016045:Human Genome Project; D006801:Humans; D007438:Introns / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics*; D012322:RNA Precursors; D022821:RNA Splice Sites / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D012322:RNA Precursors; D022821:RNA Splice Sites