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- W2203233036 abstract "One mechanism of resistance of the melanoma-associated BRAF kinase to its small molecule inhibitor vemurafenib is by point mutations in its intron 8 resulting in exons 4–8 skipping. In this report, we carried out in vitro BRAF RNA splicing assays and lariat RT-PCR to map the intron 8 branch points in wild-type and BRAF mutants. We identify multiple branch points (BP) in intron 8 of both wild-type (wt) and vemurafenib-resistant BRAF RNA. In wt BRAF, BPs are located at -29A, -28A and -26A, whereas in a vemurafenib-resistant BRAF splicing mutant, BPs map to -22A, -18A and -15A, proximal to the intron 8 3′ splice site. This finding of a distal-to-proximal shift of the branch point sequence in BRAF splicing in response to point-mutations in intron 8 provides insight into the regulation of BRAF alternative splicing upon vemurafenib resistance." @default.
- W2203233036 created "2016-06-24" @default.
- W2203233036 creator A5031894721 @default.
- W2203233036 creator A5086610984 @default.
- W2203233036 date "2015-12-01" @default.
- W2203233036 modified "2023-10-16" @default.
- W2203233036 title "Vemurafenib-resistant BRAF selects alternative branch points different from its wild-type BRAF in intron 8 for RNA splicing" @default.
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- W2203233036 doi "https://doi.org/10.1186/s13578-015-0061-7" @default.
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