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• W2890105589 abstract "Alternative splicing (AS) in response to changing external conditions often requires alterations in the ability of sequence-specific RNA-binding proteins to bind to cis-acting sequences in their target pre-mRNA. While daily oscillations in AS events have been described in several organisms, cis-acting sequences that control time of the day-dependent AS remain largely elusive. Here we define cis-regulatory RNA elements that control body-temperature driven rhythmic AS using the mouse U2af26 gene as a model system. We identify a complex network of cis-regulatory sequences that regulate AS of U2af26, and show that the activity of two enhancer elements is necessary for oscillating AS. A minigene comprising these U2af26 regions recapitulates rhythmic splicing of the endogenous gene, which is controlled through temperature-regulated SR protein phosphorylation. Mutagenesis of the minigene delineates the cis-acting enhancer element for SRSF2 within exon 6 to single nucleotide resolution and reveals that the combined activity of SRSF2 and SRSF7 is required for oscillating U2af26 AS. By combining RNA-Seq with an siRNA screen and individual-nucleotide resolution cross-linking and immunoprecipitation (iCLIP), we identify a complex network of SR proteins that globally controls temperature-dependent rhythmic AS, with the direction of splicing depending on the position of the cis-acting elements. Together, we provide detailed insights into the sequence requirements that allow trans-acting factors to generate daily rhythms in AS." @default.
• W2890105589 created "2018-09-27" @default.
• W2890105589 creator A5048815490 @default.
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• W2890105589 creator A5060003119 @default.
• W2890105589 creator A5075295674 @default.
• W2890105589 creator A5083377486 @default.
• W2890105589 date "2018-09-10" @default.
• W2890105589 modified "2023-10-17" @default.
• W2890105589 title "Characterization of cis-acting elements that control oscillating alternative splicing" @default.
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• W2890105589 doi "https://doi.org/10.1080/15476286.2018.1502587" @default.
• W2890105589 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6161694" @default.
• W2890105589 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30200840" @default.
• W2890105589 hasPublicationYear "2018" @default.
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