Genome-wide prediction of <it>cis</it>-acting RNA elements regulating tissue-specific pre-mRNA alternative splicing
<p>Abstract</p> <p>Background</p> <p>Human genes undergo various patterns of pre-mRNA splicing across different tissues. Such variation is primarily regulated by <it>trans</it>-acting factors that bind on exonic and intronic <it>cis</it>-acting R...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-07-01
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| Series: | BMC Genomics |
| _version_ | 1818207954246041600 |
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| author | Wang Guohua Wang Yue Radovich Milan Wang Kejun Wang Xin Feng Weixing Sanford Jeremy R Liu Yunlong |
| author_facet | Wang Guohua Wang Yue Radovich Milan Wang Kejun Wang Xin Feng Weixing Sanford Jeremy R Liu Yunlong |
| author_sort | Wang Guohua |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Human genes undergo various patterns of pre-mRNA splicing across different tissues. Such variation is primarily regulated by <it>trans</it>-acting factors that bind on exonic and intronic <it>cis</it>-acting RNA elements (CAEs). Here we report a computational method to mechanistically identify <it>cis</it>-acting RNA elements that contribute to the tissue-specific alternative splicing pattern. This method is an extension of our previous model, <it>SplicingModeler</it>, which predicts the significant CAEs that contribute to the splicing differences between two tissues. In this study, we introduce tissue-specific functional levels estimation step, which allows evaluating regulatory functions of predicted CAEs that are involved in more than two tissues.</p> <p>Results</p> <p>Using a publicly available Affymetrix Genechip<sup>® </sup>Human Exon Array dataset, our method identifies 652 <it>cis</it>-acting RNA elements (CAEs) across 11 human tissues. About one third of predicted CAEs can be mapped to the known RBP (RNA binding protein) binding sites or match with other predicted exonic splicing regulator databases. Interestingly, the vast majority of predicted CAEs are in intronic regulatory regions. A noticeable exception is that many exonic elements are found to regulate the alternative splicing between cerebellum and testes. Most identified elements are found to contribute to the alternative splicing between two tissues, while some are important in multiple tissues. This suggests that genome-wide alternative splicing patterns are regulated by a combination of tissue-specific <it>cis</it>-acting elements and "general elements" whose functional activities are important but differ across multiple tissues.</p> <p>Conclusion</p> <p>In this study, we present a model-based computational approach to identify potential <it>cis</it>-acting RNA elements by considering the exon splicing variation as the combinatorial effects of multiple <it>cis</it>-acting regulators. This methodology provides a novel evaluation on the functional levels of <it>cis</it>-acting RNA elements by estimating their tissue-specific functions on various tissues.</p> |
| first_indexed | 2024-12-12T04:37:07Z |
| format | Article |
| id | doaj.art-9d2ec96f796b48d7bed6267d3acf5c71 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-12T04:37:07Z |
| publishDate | 2009-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-9d2ec96f796b48d7bed6267d3acf5c712022-12-22T00:37:55ZengBMCBMC Genomics1471-21642009-07-0110Suppl 1S410.1186/1471-2164-10-S1-S4Genome-wide prediction of <it>cis</it>-acting RNA elements regulating tissue-specific pre-mRNA alternative splicingWang GuohuaWang YueRadovich MilanWang KejunWang XinFeng WeixingSanford Jeremy RLiu Yunlong<p>Abstract</p> <p>Background</p> <p>Human genes undergo various patterns of pre-mRNA splicing across different tissues. Such variation is primarily regulated by <it>trans</it>-acting factors that bind on exonic and intronic <it>cis</it>-acting RNA elements (CAEs). Here we report a computational method to mechanistically identify <it>cis</it>-acting RNA elements that contribute to the tissue-specific alternative splicing pattern. This method is an extension of our previous model, <it>SplicingModeler</it>, which predicts the significant CAEs that contribute to the splicing differences between two tissues. In this study, we introduce tissue-specific functional levels estimation step, which allows evaluating regulatory functions of predicted CAEs that are involved in more than two tissues.</p> <p>Results</p> <p>Using a publicly available Affymetrix Genechip<sup>® </sup>Human Exon Array dataset, our method identifies 652 <it>cis</it>-acting RNA elements (CAEs) across 11 human tissues. About one third of predicted CAEs can be mapped to the known RBP (RNA binding protein) binding sites or match with other predicted exonic splicing regulator databases. Interestingly, the vast majority of predicted CAEs are in intronic regulatory regions. A noticeable exception is that many exonic elements are found to regulate the alternative splicing between cerebellum and testes. Most identified elements are found to contribute to the alternative splicing between two tissues, while some are important in multiple tissues. This suggests that genome-wide alternative splicing patterns are regulated by a combination of tissue-specific <it>cis</it>-acting elements and "general elements" whose functional activities are important but differ across multiple tissues.</p> <p>Conclusion</p> <p>In this study, we present a model-based computational approach to identify potential <it>cis</it>-acting RNA elements by considering the exon splicing variation as the combinatorial effects of multiple <it>cis</it>-acting regulators. This methodology provides a novel evaluation on the functional levels of <it>cis</it>-acting RNA elements by estimating their tissue-specific functions on various tissues.</p> |
| spellingShingle | Wang Guohua Wang Yue Radovich Milan Wang Kejun Wang Xin Feng Weixing Sanford Jeremy R Liu Yunlong Genome-wide prediction of <it>cis</it>-acting RNA elements regulating tissue-specific pre-mRNA alternative splicing BMC Genomics |
| title | Genome-wide prediction of <it>cis</it>-acting RNA elements regulating tissue-specific pre-mRNA alternative splicing |
| title_full | Genome-wide prediction of <it>cis</it>-acting RNA elements regulating tissue-specific pre-mRNA alternative splicing |
| title_fullStr | Genome-wide prediction of <it>cis</it>-acting RNA elements regulating tissue-specific pre-mRNA alternative splicing |
| title_full_unstemmed | Genome-wide prediction of <it>cis</it>-acting RNA elements regulating tissue-specific pre-mRNA alternative splicing |
| title_short | Genome-wide prediction of <it>cis</it>-acting RNA elements regulating tissue-specific pre-mRNA alternative splicing |
| title_sort | genome wide prediction of it cis it acting rna elements regulating tissue specific pre mrna alternative splicing |
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