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- W2118004539 endingPage "1821" @default.
- W2118004539 startingPage "1812" @default.
- W2118004539 abstract "Regulation of tau exon 10 splicing plays an important role in tauopathy. One of the cis elements regulating tau alternative splicing is a stem-loop structure at the 5' splice site of tau exon 10. The RNA helicase(s) modulating this stem-loop structure was unknown. We searched for splicing regulators interacting with this stem-loop region using an RNA affinity pulldown-coupled mass spectrometry approach and identified DDX5/RNA helicase p68 as an activator of tau exon 10 splicing. The activity of p68 in stimulating tau exon 10 inclusion is dependent on RBM4, an intronic splicing activator. RNase H cleavage and U1 protection assays suggest that p68 promotes conformational change of the stem-loop structure, thereby increasing the access of U1snRNP to the 5' splice site of tau exon 10. This study reports the first RNA helicase interacting with a stem-loop structure at the splice site and regulating alternative splicing in a helicase-dependent manner. Our work uncovers a previously unknown function of p68 in regulating tau exon 10 splicing. Furthermore, our experiments reveal functional interaction between two splicing activators for tau exon 10, p68 binding at the stem-loop region and RBM4 interacting with the intronic splicing enhancer region." @default.
- W2118004539 created "2016-06-24" @default.
- W2118004539 creator A5002460182 @default.
- W2118004539 creator A5003229372 @default.
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- W2118004539 creator A5017221404 @default.
- W2118004539 creator A5059007081 @default.
- W2118004539 creator A5083553557 @default.
- W2118004539 creator A5089677197 @default.
- W2118004539 creator A5091070290 @default.
- W2118004539 date "2011-05-01" @default.
- W2118004539 modified "2023-09-30" @default.
- W2118004539 title "RNA Helicase p68 (DDX5) Regulates <i>tau</i> Exon 10 Splicing by Modulating a Stem-Loop Structure at the 5′ Splice Site" @default.
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