title: Long-range RNA pairings contribute to mutually exclusive splicing.
abstract: Mutually exclusive splicing is an important means of increasing the protein repertoire, by which the Down's syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 different isoforms in Drosophila melanogaster. However, the regulatory mechanisms remain obscure due to the complexity of the Dscam exon cluster. Here, we reveal a molecular model for the regulation of the mutually exclusive splicing of the serpent pre-mRNA based on competition between upstream and downstream RNA pairings. Such dual RNA pairings confer fine tuning of the inclusion of alternative exons. Moreover, we demonstrate that the splicing outcome of alternative exons is mediated in relative pairing strength-correlated mode. Combined comparative genomics analysis and experimental evidence revealed similar bidirectional structural architectures in exon clusters 4 and 9 of the Dscam gene. Our findings provide a novel mechanistic framework for the regulation of mutually exclusive splicing and may offer potentially applicable insights into long-range RNA-RNA interactions in gene regulatory networks.
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus), Hangzhou, Zhejiang, ZJ310058, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yue
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus), Hangzhou, Zhejiang, ZJ310058, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus), Hangzhou, Zhejiang, ZJ310058, China.
authors.forename: Lanzhi
authors.initials: L
authors.lastname: Dai
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus), Hangzhou, Zhejiang, ZJ310058, China.
authors.forename: Guozheng
authors.initials: G
authors.lastname: Cao
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus), Hangzhou, Zhejiang, ZJ310058, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Chen
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus), Hangzhou, Zhejiang, ZJ310058, China.
authors.forename: Weiling
authors.initials: W
authors.lastname: Hong
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus), Hangzhou, Zhejiang, ZJ310058, China.
authors.forename: Baoping
authors.initials: B
authors.lastname: Liu
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus), Hangzhou, Zhejiang, ZJ310058, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus), Hangzhou, Zhejiang, ZJ310058, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus), Hangzhou, Zhejiang, ZJ310058, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Shi
authors.affiliation: Institute of Life Sciences, Zhejiang University (Zijingang Campus), Hangzhou, Zhejiang, ZJ310058, China.
authors.forename: Mu
authors.initials: M
authors.lastname: Xiao
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus), Hangzhou, Zhejiang, ZJ310058, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Jin
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster; D005091:Exons; D008969:Molecular Sequence Data; D012313:RNA / Q000235:genetics*
chemical_list: D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C491736:Dscam1 protein, Drosophila; D012313:RNA
keywords: Dscam; bidirectional RNA pairing; mutually exclusive splicing; regulatory mechanism; serpent