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Open Access Highly Accessed Research article

Sequence features responsible for intron retention in human

Noboru Jo Sakabe12 and Sandro José de Souza1*

Author Affiliations

1 Ludwig Institute for Cancer Research, Sao Paulo Branch, Hospital Alemão Oswaldo Cruz, Rua João Julião, 245 – 1° andar, CEP 01323-903, São Paulo, SP, Brazil

2 PhD. Program, Departamento de Bioquímica, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748 – Bloco 03 superior, sala 351, CEP: 05508-900, Cidade Universitária, São Paulo, SP, Brazil

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BMC Genomics 2007, 8:59  doi:10.1186/1471-2164-8-59

Published: 26 February 2007

Abstract

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.

Conclusion

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.