The RNA splicing factor topoisomerase I mediated SF/SF2 inhibits human DNA relaxation
The RNA splicing factor topoisomerase I mediated SF/SF2 inhibits human DNA relaxation
复制标题
DOI：
10.1016/s0022-2836(02)00815-x
复制
发表时间：
2002-09-27
影响因子：
5.6
通讯作者：
Knudsen, BR
中科院分区：
文献类型：
--
作者：
Andersen, FF;Tange, TO;Knudsen, BR
人拓扑异构酶 I 与 RNA 剪接因子 SR 家族（包括 ASF/SF2）相互作用并使其磷酸化，并被认为在 RNA 剪接的调节中发挥重要作用。在这里，我们提供证据支持这一理论，即调节可以与控制拓扑异构酶 I DNA 活性的 SR 蛋白相反。我们证明剪接因子 ASF/SF2 通过干扰人拓扑异构酶 I 催化的 DNA 切割和/或 DNA 结合步骤来抑制松弛。松弛的抑制与两种蛋白质的各种缺失突变体直接相互作用的能力相关，表明ASF/SF2的RS结构域与拓扑异构酶I上氨基酸残基208-735之间的区域之间的相互作用解释了观察到的效果。一致地，拓扑异构酶 I 或人细胞提取物对 RS 结构域的磷酸化减少了对松弛活性的抑制。结合之前发表的拓扑异构酶 I 激酶活性研究，这些观察结果表明拓扑异构酶 I 活性通过与 SR 剪接因子的特异性相互作用从松弛转变为激酶。 (C) 2002 Elsevier Science Ltd. 保留所有权利。
Human topoisomerase I interacts with and phosphorylates the SR-family of RNA splicing factors, including ASF/SF2, and has been suggested to play an important role in the regulation of RNA splicing. Here we present evidence to support the theory that the regulation can go the other way around with the SR-proteins controlling topoisomerase I DNA activity. We demonstrate that the splicing factor ASF/SF2 inhibits relaxation by interfering with the DNA cleavage and/or DNA binding steps of human topoisomerase I catalysis. The inhibition of relaxation correlated with the ability of various deletion mutants of the two proteins to interact directly, suggesting that an interaction between the RS-domain of ASF/SF2 and a region between amino acid residues 208-735 on topoisomerase I accounts for the observed effect. Consistently, phosphorylation of the RS-domain with either topoisomerase I or a human cell extract reduced the inhibition of relaxation activity. Taken together with the previously published studies of the topoisomerase I kinase activity, these observations suggest that topoisomerase I activity is shifted from relaxation to kinasing by specific interaction with SR-splicing factors. (C) 2002 Elsevier Science Ltd. All rights reserved.