Sequence features responsible for intron retention in human.
BACKGROUND
One of the least common types of alternative splicing is the complete retention of an intron in a mature transcript. Intron retention (IR) is believed to be the result of intron, rather than exon, definition associated with failure of the recognition of weak splice sites flanking short introns. Although studies on individual retained introns have been published, few systematic surveys of large amounts of data have been conducted on the mechanisms that lead to IR.


RESULTS
TTo understand how sequence features are associated with or control IR, and to produce a generalized model that could reveal previously unknown signals that regulate this type of alternative splicing, we partitioned intron retention events observed in human cDNAs into two groups based on the relative abundance of both isoforms and compared relevant features. We found that a higher frequency of IR in human is associated with individual introns that have weaker splice sites, genes with shorter intron lengths, higher expression levels and lower density of both a set of exon splicing silencers (ESSs) and the intronic splicing enhancer GGG. Both groups of retained introns presented events conserved in mouse, in which the retained introns were also short and presented weaker splice sites.


CONCLUSIONS
Although our results confirmed that weaker splice sites are associated with IR, they showed that this feature alone cannot explain a non-negligible fraction of events. Our analysis suggests that cis-regulatory elements are likely to play a crucial role in regulating IR and also reveals previously unknown features that seem to influence its occurrence. These results highlight the importance of considering the interplay among these features in the regulation of the relative frequency of IR.
Sakabe
Noboru Jo
NJ
Ludwig Institute for Cancer Research, Sao Paulo Branch, Hospital Alemão Oswaldo Cruz, CEP 01323-903, São Paulo, SP, Brazil. noboru@iq.usp.br <noboru@iq.usp.br>
de Souza
Sandro José
SJ
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary; D004742:Enhancer Elements, Genetic; D006801:Humans; D007438:Introns / Q000235:genetics*; D051379:Mice; D022821:RNA Splice Sites
D018076:DNA, Complementary; D022821:RNA Splice Sites