Regulation of Dscam exon 17 alternative splicing by steric hindrance in combination with RNA secondary structures.
The gene Down syndrome cell adhesion molecule (Dscam) potentially encodes 38 016 distinct isoforms in Drosophila melanogaster via mutually exclusive splicing. Here we reveal a combinatorial mechanism of regulation of Dscam exon 17 mutually exclusive splicing through steric hindrance in combination with RNA secondary structure. This mutually exclusive behavior is enforced by steric hindrance, due to the close proximity of the exon 17.2 branch point to exon 17.1 in Diptera, and the interval size constraint in non-Dipteran species. Moreover, intron-exon RNA structures are evolutionarily conserved in 36 non-Drosophila species of six distantly related orders (Diptera, Lepidoptera, Coleoptera, Hymenoptera, Hemiptera, and Phthiraptera), which regulates the selection of exon 17 variants via masking the splice site. By contrast, a previously uncharacterized RNA structure specifically activated exon 17.1 by bringing splice sites closer together in Drosophila, while the other moderately suppressed exon 17.1 selection by hindering the accessibility of polypyrimidine sequences. Taken together, these data suggest a phylogeny of increased complexity in regulating alternative splicing of Dscam exon 17 spanning more than 300 million years of insect evolution. These results also provide models of the regulation of alternative splicing through steric hindrance in combination with dynamic structural codes.
Institute of Biochemistry; College of Life Sciences; Zhejiang University (Zijingang Campus); Hangzhou; Zhejiang, PR China.
Yuan
Y
Yue
Institute of Biochemistry; College of Life Sciences; Zhejiang University (Zijingang Campus); Hangzhou; Zhejiang, PR China.
Guoli
G
Li
Institute of Biochemistry; College of Life Sciences; Zhejiang University (Zijingang Campus); Hangzhou; Zhejiang, PR China.
Yun
Y
Yang
Institute of Biochemistry; College of Life Sciences; Zhejiang University (Zijingang Campus); Hangzhou; Zhejiang, PR China.
Wenjing
W
Zhang
Institute of Biochemistry; College of Life Sciences; Zhejiang University (Zijingang Campus); Hangzhou; Zhejiang, PR China.
Huawei
H
Pan
Institute of Biochemistry; College of Life Sciences; Zhejiang University (Zijingang Campus); Hangzhou; Zhejiang, PR China.
Ran
R
Chen
Institute of Biochemistry; College of Life Sciences; Zhejiang University (Zijingang Campus); Hangzhou; Zhejiang, PR China.
Feng
F
Shi
Institute of Biochemistry; College of Life Sciences; Zhejiang University (Zijingang Campus); Hangzhou; Zhejiang, PR China.
Yongfeng
Y
Jin
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons; D005786:Gene Expression Regulation; D019476:Insect Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D007313:Insecta / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D007438:Introns; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics
D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C491736:Dscam1 protein, Drosophila; D019476:Insect Proteins; D020033:Protein Isoforms; D022821:RNA Splice Sites
Dscamexon 17; RNA secondary structures; evolution; mutually exclusive splicing; steric hindrance