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- W4252222489 abstract "Abstract The Drosophila melanogaster LS2 protein is a tissue-specific paralog of U2AF2 that mediates testis-specific alternative splicing. In order to understand the structural mechanisms underlying the distinct RNA binding specificity we determined the solution structures of the LS2 RNA recognition motif (RRM) domains and characterized their interaction with cis -regulatory guanosine-rich RNA motifs found in intron regions upstream of alternatively spliced exons. We show that the guanosine-rich RNA adopts a G quadruplex (G4) fold in vitro . The LS2 tandem RRMs adopt canonical RRM folds that are connected by a 38-residue linker that harbors a small helical motif α 0 . The LS2 RRM2 domain and the α 0 helix in the interdomain linker mediate interactions with the G4 RNA. The functional importance of these unique molecular features in LS2 is validated by mutational analysis in vitro and RNA splicing assays in vivo . RNA sequencing data confirm the enrichment of G4-forming LS2 target motifs near LS2-affected exons. Our data indicate a role of G quadruplex structures as cis -regulatory motifs in introns for the regulation of alternative splicing, that engage non-canonical interactions with a tandem RRM protein. These results highlight the intriguing molecular evolution of a tissue-specific splicing factor from its conserved U2AF2 paralog as a result of (retro-) gene duplication in D. melanogaster ." @default.
- W4252222489 created "2022-05-12" @default.
- W4252222489 creator A5013491427 @default.
- W4252222489 creator A5034073565 @default.
- W4252222489 creator A5046686387 @default.
- W4252222489 creator A5048799588 @default.
- W4252222489 creator A5053668530 @default.
- W4252222489 creator A5058741299 @default.
- W4252222489 creator A5080019048 @default.
- W4252222489 creator A5083102983 @default.
- W4252222489 creator A5083161922 @default.
- W4252222489 date "2020-08-15" @default.
- W4252222489 modified "2023-09-26" @default.
- W4252222489 title "Structural evolution of the tissue-specific U2AF2 paralog and alternative splicing factor LS2" @default.
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