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Computational prediction of splicing regulatory elements shared by Tetrapoda organisms

Computational prediction of splicing regulatory elements shared by Tetrapoda organisms
Computational prediction of splicing regulatory elements shared by Tetrapoda organisms
Background: auxiliary splicing sequences play an important role in ensuring accurate and efficient splicing by promoting or repressing recognition of authentic splice sites. These cis-acting motifs have been termed splicing enhancers and silencers and are located both in introns and exons. They co-evolved into an intricate splicing code together with additional functional constraints, such as tissue-specific and alternative splicing patterns. We used orthologous exons extracted from the University of California Santa Cruz multiple genome alignments of human and 22 Tetrapoda organisms to predict candidate enhancers and silencers that have reproducible and statistically significant bias towards annotated exonic boundaries.
Results: a total of 2,546 Tetrapoda enhancers and silencers were clustered into 15 putative core motifs based on their Markov properties. Most of these elements have been identified previously, but 118 putative silencers and 260 enhancers (~15%) were novel. Examination of previously published experimental data for the presence of predicted elements showed that their mutations in 21/23 (91.3%) cases altered the splicing pattern as expected. Predicted intronic motifs flanking 3' and 5' splice sites had higher evolutionary conservation than other sequences within intronic flanks and the intronic enhancers were markedly differed between 3' and 5' intronic flanks.
Conclusion: difference in intronic enhancers supporting 5' and 3' splice sites suggests an independent splicing commitment for neighboring exons. Increased evolutionary conservation for ISEs/ISSs within intronic flanks and effect of modulation of predicted elements on splicing suggest functional significance of found elements in splicing regulation. Most of the elements identified were shown to have direct implications in human splicing and therefore could be useful for building computational splicing models in biomedical research
1471-2164
508
Churbanov, Alexander
3ef4f6a4-211f-418c-9c4f-7b88de55da12
Vořechovský, Igor
7245de2f-8c9b-4034-8935-9a451d9b682e
Hicks, Chindo
5be4f446-3bfd-4992-9c01-738e19bcd466
Churbanov, Alexander
3ef4f6a4-211f-418c-9c4f-7b88de55da12
Vořechovský, Igor
7245de2f-8c9b-4034-8935-9a451d9b682e
Hicks, Chindo
5be4f446-3bfd-4992-9c01-738e19bcd466

Churbanov, Alexander, Vořechovský, Igor and Hicks, Chindo (2009) Computational prediction of splicing regulatory elements shared by Tetrapoda organisms. BMC Genomics, 10, 508. (doi:10.1186/1471-2164-10-508).

Record type: Article

Abstract

Background: auxiliary splicing sequences play an important role in ensuring accurate and efficient splicing by promoting or repressing recognition of authentic splice sites. These cis-acting motifs have been termed splicing enhancers and silencers and are located both in introns and exons. They co-evolved into an intricate splicing code together with additional functional constraints, such as tissue-specific and alternative splicing patterns. We used orthologous exons extracted from the University of California Santa Cruz multiple genome alignments of human and 22 Tetrapoda organisms to predict candidate enhancers and silencers that have reproducible and statistically significant bias towards annotated exonic boundaries.
Results: a total of 2,546 Tetrapoda enhancers and silencers were clustered into 15 putative core motifs based on their Markov properties. Most of these elements have been identified previously, but 118 putative silencers and 260 enhancers (~15%) were novel. Examination of previously published experimental data for the presence of predicted elements showed that their mutations in 21/23 (91.3%) cases altered the splicing pattern as expected. Predicted intronic motifs flanking 3' and 5' splice sites had higher evolutionary conservation than other sequences within intronic flanks and the intronic enhancers were markedly differed between 3' and 5' intronic flanks.
Conclusion: difference in intronic enhancers supporting 5' and 3' splice sites suggests an independent splicing commitment for neighboring exons. Increased evolutionary conservation for ISEs/ISSs within intronic flanks and effect of modulation of predicted elements on splicing suggest functional significance of found elements in splicing regulation. Most of the elements identified were shown to have direct implications in human splicing and therefore could be useful for building computational splicing models in biomedical research

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Published date: 4 November 2009

Identifiers

Local EPrints ID: 69805
URI: http://eprints.soton.ac.uk/id/eprint/69805
ISSN: 1471-2164
PURE UUID: 47f2ddbc-18de-4f69-8805-aa69eb897fe1
ORCID for Igor Vořechovský: ORCID iD orcid.org/0000-0002-6740-6502

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Date deposited: 07 Dec 2009
Last modified: 14 Mar 2024 02:48

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Author: Alexander Churbanov
Author: Chindo Hicks

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