title: RNA secondary structure in mutually exclusive splicing.
abstract: Mutually exclusive splicing is a regulated means to generate protein diversity, but the underlying mechanisms are poorly understood. Here comparative genome analysis revealed the built-in intronic elements for controlling mutually exclusive splicing of the 14-3-3ξ pre-mRNA. These elements are clade specific but are evolutionarily conserved at the secondary structure level. Combined evidence revealed the triple functions of these inter-intronic RNA pairings in synergistically ensuring the selection of only one of multiple exons, through activation of the proximal variable exon outside the loop by the approximation of cis elements, and simultaneous repression of the exon within the loop, in combination with the physical competition of RNA pairing. Additionally, under this model, we also deciphered a similar structural code in exon clusters 4 and 9 of Dscam (38,016 isoforms) and Mhc (480 isoforms). Our findings suggest a broadly applicable mechanism to ensure mutually exclusive splicing.
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus), Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yang
authors.forename: Leilei
authors.initials: L
authors.lastname: Zhan
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Sun
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Tian
authors.forename: Jingpei
authors.initials: J
authors.lastname: Bi
authors.forename: Haitao
authors.initials: H
authors.lastname: Wang
authors.forename: Dike
authors.initials: D
authors.lastname: Shi
authors.forename: Yajian
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yaozhou
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000818:Animals; D001483:Base Sequence; D004330:Drosophila / Q000737:chemistry / Q000235:genetics*; D005091:Exons; D017344:Genes, Insect; D007438:Introns; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D012322:RNA Precursors / Q000737:chemistry* / Q000235:genetics*; D012326:RNA Splicing; D016415:Sequence Alignment
chemical_list: D012322:RNA Precursors