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An RNA architectural locus control region involved in Dscam mutually exclusive splicing
The most striking example of alternative splicing in a Drosophila melanogaster gene is observed in the Down syndrome cell adhesion molecule, which can generate 38,016 different isoforms. RNA secondary structures are thought to direct the mutually exclusive splicing of Down syndrome cell adhesion mol...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535345/ https://www.ncbi.nlm.nih.gov/pubmed/23212384 http://dx.doi.org/10.1038/ncomms2269 |
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author | Wang, Xuebin Li, Guoli Yang, Yun Wang, Wenfeng Zhang, Wenjing Pan, Huawei Zhang, Peng Yue, Yuan Lin, Hao Liu, Baoping Bi, Jingpei Shi, Feng Mao, Jinping Meng, Yijun Zhan, Leilei Jin, Yongfeng |
author_facet | Wang, Xuebin Li, Guoli Yang, Yun Wang, Wenfeng Zhang, Wenjing Pan, Huawei Zhang, Peng Yue, Yuan Lin, Hao Liu, Baoping Bi, Jingpei Shi, Feng Mao, Jinping Meng, Yijun Zhan, Leilei Jin, Yongfeng |
author_sort | Wang, Xuebin |
collection | PubMed |
description | The most striking example of alternative splicing in a Drosophila melanogaster gene is observed in the Down syndrome cell adhesion molecule, which can generate 38,016 different isoforms. RNA secondary structures are thought to direct the mutually exclusive splicing of Down syndrome cell adhesion molecule, but the underlying mechanisms are poorly understood. Here we describe a locus control region that can activate the exon 6 cluster and specifically allow for the selection of only one exon variant in combination with docking site selector sequence interactions. Combining comparative genomic studies of 63 species with mutational analysis reveals that intricate, tandem multi-‘subunit’ RNA structures within the locus control region activate species-appropriate alternative variants. Importantly, strengthening the weak splice sites of the target exon can remove the locus control region dependence. Our findings not only provide a locus control region-dependent mechanism for mutually exclusive splicing, but also suggest a model for the evolution of increased complexity in a long-range RNA molecular machine. |
format | Online Article Text |
id | pubmed-3535345 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-35353452013-01-03 An RNA architectural locus control region involved in Dscam mutually exclusive splicing Wang, Xuebin Li, Guoli Yang, Yun Wang, Wenfeng Zhang, Wenjing Pan, Huawei Zhang, Peng Yue, Yuan Lin, Hao Liu, Baoping Bi, Jingpei Shi, Feng Mao, Jinping Meng, Yijun Zhan, Leilei Jin, Yongfeng Nat Commun Article The most striking example of alternative splicing in a Drosophila melanogaster gene is observed in the Down syndrome cell adhesion molecule, which can generate 38,016 different isoforms. RNA secondary structures are thought to direct the mutually exclusive splicing of Down syndrome cell adhesion molecule, but the underlying mechanisms are poorly understood. Here we describe a locus control region that can activate the exon 6 cluster and specifically allow for the selection of only one exon variant in combination with docking site selector sequence interactions. Combining comparative genomic studies of 63 species with mutational analysis reveals that intricate, tandem multi-‘subunit’ RNA structures within the locus control region activate species-appropriate alternative variants. Importantly, strengthening the weak splice sites of the target exon can remove the locus control region dependence. Our findings not only provide a locus control region-dependent mechanism for mutually exclusive splicing, but also suggest a model for the evolution of increased complexity in a long-range RNA molecular machine. Nature Pub. Group 2012-12-04 /pmc/articles/PMC3535345/ /pubmed/23212384 http://dx.doi.org/10.1038/ncomms2269 Text en Copyright © 2012, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
spellingShingle | Article Wang, Xuebin Li, Guoli Yang, Yun Wang, Wenfeng Zhang, Wenjing Pan, Huawei Zhang, Peng Yue, Yuan Lin, Hao Liu, Baoping Bi, Jingpei Shi, Feng Mao, Jinping Meng, Yijun Zhan, Leilei Jin, Yongfeng An RNA architectural locus control region involved in Dscam mutually exclusive splicing |
title | An RNA architectural locus control region involved in Dscam mutually exclusive splicing |
title_full | An RNA architectural locus control region involved in Dscam mutually exclusive splicing |
title_fullStr | An RNA architectural locus control region involved in Dscam mutually exclusive splicing |
title_full_unstemmed | An RNA architectural locus control region involved in Dscam mutually exclusive splicing |
title_short | An RNA architectural locus control region involved in Dscam mutually exclusive splicing |
title_sort | rna architectural locus control region involved in dscam mutually exclusive splicing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535345/ https://www.ncbi.nlm.nih.gov/pubmed/23212384 http://dx.doi.org/10.1038/ncomms2269 |
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