title: A regulator of Dscam mutually exclusive splicing fidelity.
abstract: The Down syndrome cell adhesion molecule (Dscam) gene has essential roles in neural wiring and pathogen recognition in Drosophila melanogaster. Dscam encodes 38,016 distinct isoforms via extensive alternative splicing. The 95 alternative exons in Dscam are organized into clusters that are spliced in a mutually exclusive manner. The exon 6 cluster contains 48 variable exons and uses a complex system of competing RNA structures to ensure that only one variable exon is included. Here we show that the heterogeneous nuclear ribonucleoprotein hrp36 acts specifically within, and throughout, the exon 6 cluster to prevent the inclusion of multiple exons. Moreover, hrp36 prevents serine/arginine-rich proteins from promoting the ectopic inclusion of multiple exon 6 variants. Thus, the fidelity of mutually exclusive splicing in the exon 6 cluster is governed by an intricate combination of alternative RNA structures and a globally acting splicing repressor.
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, Connecticut 06030-3301, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Olson
authors.forename: Marco
authors.initials: M
authors.lastname: Blanchette
authors.forename: Jung
authors.initials: J
authors.lastname: Park
authors.forename: Yiannis
authors.initials: Y
authors.lastname: Savva
authors.forename: Gene W
authors.initials: GW
authors.lastname: Yeo
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Yeakley
authors.forename: Donald C
authors.initials: DC
authors.lastname: Rio
authors.forename: Brenton R
authors.initials: BR
authors.lastname: Graveley
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics; D005091:Exons / Q000235:genetics*; D005786:Gene Expression Regulation; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000502:physiology*; D006801:Humans; D009687:Nuclear Proteins; D040081:Protein Array Analysis; D022821:RNA Splice Sites / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C491736:Dscam1 protein, Drosophila; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C402657:Hrb87F protein, Drosophila; D009687:Nuclear Proteins; D022821:RNA Splice Sites; D012333:RNA, Messenger