An RNA architectural locus control region involved in Dscam mutually exclusive splicing
| Autor: | Jinping Mao, Baoping Liu, Guoli Li, Wenfeng Wang, Huawei Pan, Jingpei Bi, Peng Zhang, Yijun Meng, Yun Yang, Yuan Yue, Xuebin Wang, Feng Shi, Hao Lin, Yongfeng Jin, Leilei Zhan, Wenjing Zhang |
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| Rok vydání: | 2012 |
| Předmět: |
Molecular Sequence Data
Exonic splicing enhancer General Physics and Astronomy Biology Article General Biochemistry Genetics and Molecular Biology Evolution Molecular Exon DSCAM Animals Drosophila Proteins Gene Conserved Sequence Locus control region Genetics Multidisciplinary Alternative splicing Intron Exons General Chemistry Locus Control Region Hymenoptera Alternative Splicing Drosophila melanogaster Enhancer Elements Genetic Daphnia RNA splicing Nucleic Acid Conformation RNA Cell Adhesion Molecules |
| Zdroj: | Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms2269 |
| Popis: | 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. Alternative splicing at the Drosophila Down syndrome cell adhesion molecule gene generates 38,016 isoforms, and underlies self-avoidance of growing neurons. Wang et al. identify a structure in the DSCAM mRNA that ensures mutually exclusive splicing and observe expansion of the structure with increasing number of exons during arthropod evolution. |
| Databáze: | OpenAIRE |
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