Abstract
BackgroundMost 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.ResultsThe 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.ConclusionThus 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.
Highlights
Most retained introns found in human cDNAs generated by high-throughput sequencing projects seem to result from underspliced transcripts, and they capture intermediate steps of pre-mRNA splicing
Comparison of retained and constitutive introns Sets of retained (Fig. 1) and constitutive introns were constructed as described in Data and Methods and compared with the aim to identify possible determinants of intron retention
We considered the distribution of intron lengths and of lengths of the flanking exons, scores of intron splice sites and the distal sites in the flanking exons, densities of exonic cis-acting elements, intron positions within the gene
Summary
Most retained introns found in human cDNAs generated by high-throughput sequencing projects seem to result from underspliced transcripts, and they capture intermediate steps of pre-mRNA splicing. 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. The introns of lower eukaryotes, invertebrates and plants are much shorter. This difference may be explained by the preference for two possible mechanisms for recognition of the exon-intron boundaries by the splicing machinery. In the case of long introns, the exon definition mechanism initially recognizes pairs of splicing sites corresponding to one exon. Short introns are recognized by the intron definition that pairs splicing sites across introns [1]. The intron definition mechanism seems to be the ancestral one, whereas exon definition likely is a relatively (page number not for citation purposes)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
