title: 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.
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus), Hangzhou, Zhejiang ZJ310058, China.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Wang
authors.forename: Guoli
authors.initials: G
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Yang
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Wang
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhang
authors.forename: Huawei
authors.initials: H
authors.lastname: Pan
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yue
authors.forename: Hao
authors.initials: H
authors.lastname: Lin
authors.forename: Baoping
authors.initials: B
authors.lastname: Liu
authors.forename: Jingpei
authors.initials: J
authors.lastname: Bi
authors.forename: Feng
authors.initials: F
authors.lastname: Shi
authors.forename: Jinping
authors.initials: J
authors.lastname: Mao
authors.forename: Yijun
authors.initials: Y
authors.lastname: Meng
authors.forename: Leilei
authors.initials: L
authors.lastname: Zhan
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Jin
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D015815:Cell Adhesion Molecules / Q000187:drug effects*; D017124:Conserved Sequence / Q000235:genetics; D003621:Daphnia / Q000235:genetics; D029721:Drosophila Proteins / Q000187:drug effects*; D004331:Drosophila melanogaster / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D006927:Hymenoptera / Q000235:genetics; D019901:Locus Control Region / Q000235:genetics*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012313:RNA / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C491736:Dscam1 protein, Drosophila; D012313:RNA