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Open Access Research article

Sequence features involved in the mechanism of 3' splice junction wobbling

Kuo-Wang Tsai1, Wen-Ching Chan234, Chun-Nan Hsu45 and Wen-chang Lin13*

Author Affiliations

1 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

2 Bioinformatics Program, Taiwan International Graduate Program, Academia Sinica, Taipei, Taiwan

3 Institute of Bioinformatics, School of Medicine, National Yang-Ming University, Taipei, Taiwan

4 Institute of Information Sciences, Academia Sinica, Taipei, Taiwan

5 Information Sciences Institute, University of Southern California, Marina del Rey, CA, USA

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BMC Molecular Biology 2010, 11:34  doi:10.1186/1471-2199-11-34

Published: 7 May 2010

Abstract

Background

Alternative splicing is an important mechanism mediating the diversified functions of genes in multicellular organisms, and such event occurs in around 40-60% of human genes. Recently, a new splice-junction wobbling mechanism was proposed that subtle modifications exist in mRNA maturation by alternatively choosing at 5'- GTNGT and 3'- NAGNAG, which created single amino acid insertion and deletion isoforms.

Results

By browsing the Alternative Splicing Database information, we observed that most 3' alternative splice site choices occur within six nucleotides of the dominant splice site and the incidence significantly decreases further away from the dominant acceptor site. Although a lower frequency of alternative splicing occurs within the intronic region (alternative splicing at the proximal AG) than in the exonic region (alternative splicing at the distal AG), alternative AG sites located within the intronic region show stronger potential as the acceptor. These observations revealed that the choice of 3' splice sites during 3' splicing junction wobbling could depend on the distance between the duplicated AG and the branch point site (BPS). Further mutagenesis experiments demonstrated that the distance of AG-to-AG and BPS-to-AG can greatly influence 3' splice site selection. Knocking down a known alternative splicing regulator, hSlu7, failed to affect wobble splicing choices.

Conclusion

Our results implied that nucleotide distance between proximal and distal AG sites has an important regulatory function. In this study, we showed that occurrence of 3' wobble splicing occurs in a distance-dependent manner and that most of this wobble splicing is probably caused by steric hindrance from a factor bound at the neighboring tandem motif sequence.