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An RNA architectural locus control region involved in Dscam mutually exclusive splicing.


ABSTRACT: 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.

SUBMITTER: Wang X 

PROVIDER: S-EPMC3535345 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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An RNA architectural locus control region involved in Dscam mutually exclusive splicing.

Wang Xuebin X   Li Guoli G   Yang Yun Y   Wang Wenfeng W   Zhang Wenjing W   Pan Huawei H   Zhang Peng P   Yue Yuan Y   Lin Hao H   Liu Baoping B   Bi Jingpei J   Shi Feng F   Mao Jinping J   Meng Yijun Y   Zhan Leilei L   Jin Yongfeng Y  

Nature communications 20120101


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 varia  ...[more]

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