Cancer-associated mutations in SF3B1 disrupt the interaction between SF3B1 and DDX42
Cancer-associated mutations in SF3B1 disrupt the interaction between SF3B1 and DDX42
复制标题
SF3B1 的癌症相关突变破坏了 SF3B1 和 DDX42 之间的相互作用
DOI：
10.1093/jb/mvac049
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发表时间：
2022
影响因子：
2.7
通讯作者：
Youzhong Wan
中科院分区：
文献类型：
--
作者：
Bo Zhao;Zhuang Li;Rui Qian;Gang Liu;Mingyue Fan;Zehua Liang;Xin Hu;Youzhong Wan
虽然癌症相关的 SF3B1 突变会导致选择性 RNA 剪接，但选择性 RNA 剪接背后的分子机制尚未完全阐明。在这里，我们分析了与野生型和 K700E 突变的 SF3B1 相互作用的蛋白质，发现两个 RNA 解旋酶 DDX42 和 DDX46 与突变的 SF3B1 的相互作用减少。 DDX42的过表达恢复了DDX42和K700E突变的SF3B1之间减少的相互作用，并抑制了与SF3B1突变相关的一些替代RNA剪接。降低DDX42 ATP水解活性的突变消除了DDX42对可变RNA剪接的抑制作用，表明DDX42的ATP水解活性参与了与SF3B1突变相关的RNA剪接改变的机制。我们的研究证明了DDX42和SF3B1之间的相互作用在调节RNA剪接方面的重要功能，并揭示了DDX42在与SF3B1突变相关的RNA剪接改变中的潜在作用。
While cancer-associatedSF3B1mutations causes alternative RNA splicing, the molecular mechanism underlying the alternative RNA splicing is not fully elucidated. Here, we analysed the proteins that interacted with the wild-type and K700E-mutatedSF3B1and found that the interactions of two RNA helicases,DDX42andDDX46, with the mutatedSF3B1were reduced. Overexpression ofDDX42restored the decreased interaction betweenDDX42and the K700E-mutatedSF3B1, and suppressed some alternative RNA splicing associated with theSF3B1mutation. Mutation that decreased the ATP hydrolysis activities ofDDX42abolished the suppressive effects ofDDX42on the alternative RNA splicing, suggesting that the ATP hydrolysis activity ofDDX42is involved in the mechanism of the altered RNA splicing associated with theSF3B1mutation. Our study demonstrates an important function of the interaction betweenDDX42andSF3B1on regulating RNA splicing and revealed a potential role ofDDX42in the altered RNA splicing associated with theSF3B1mutation.