Mutually exclusive splicing of the insect Dscam pre-mRNA directed by competing intronic RNA secondary structures.
Drosophila Dscam encodes 38,016 distinct axon guidance receptors through the mutually exclusive alternative splicing of 95 variable exons. Importantly, known mechanisms that ensure the mutually exclusive splicing of pairs of exons cannot explain this phenomenon in Dscam. I have identified two classes of conserved elements in the Dscam exon 6 cluster, which contains 48 alternative exons--the docking site, located in the intron downstream of constitutive exon 5, and the selector sequences, which are located upstream of each exon 6 variant. Strikingly, each selector sequence is complementary to a portion of the docking site, and this pairing juxtaposes one, and only one, alternative exon to the upstream constitutive exon. The mutually exclusive nature of the docking site:selector sequence interactions suggests that the formation of these competing RNA structures is a central component of the mechanism guaranteeing that only one exon 6 variant is included in each Dscam mRNA.
Graveley
Brenton R
BR
Department of Genetics and Developmental Biology, University of Connecticut Health Center, Famington, CT 06030, USA. graveley@neuron.uchc.edu
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D015815:Cell Adhesion Molecules; D017124:Conserved Sequence / Q000235:genetics; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D007313:Insecta / Q000235:genetics / Q000378:metabolism; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity
D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C491736:Dscam1 protein, Drosophila; D012322:RNA Precursors; D012333:RNA, Messenger