Huang Tien-sheng, Nilsson Camilla Estmer, Punga Tanel, Akusjarvi Goran
Department of Medical Biochemistry and Microbiology, Uppsala University, BMC, Box 582, 751 23 Uppsala, Sweden.
EMBO Rep. 2002 Nov;3(11):1088-93. doi: 10.1093/embo-reports/kvf217. Epub 2002 Oct 22.
SR proteins are essential splicing factors required for constitutive splicing and function as key regulators of alternative RNA splicing. We have shown that SR proteins purified from late adenovirus-infected cells (SR-Ad) are functionally inactivated as splicing enhancer or splicing repressor proteins by a virus-induced partial de-phosphorylation. Here, we show that SR proteins purified from late vaccinia-virus-infected cells (SR-VV) are also hypo-phosphorylated and functionally inactivated as splicing regulatory proteins. We further show that incubating SR-Ad proteins under conditions that restore the phospho-epitopes to the SR proteins results in the restoration of their activity as splicing enhancer and splicing repressor proteins. Interestingly, re-phosphorylation of SR-VV proteins only partially restored the splicing enhancer or splicing repressor phenotype to the SR proteins. Collectively, our results suggest that viral control of SR protein activity may be a common strategy used by DNA viruses to take control of the host cell RNA splicing machinery.
SR蛋白是组成型剪接所必需的剪接因子，作为可变RNA剪接的关键调节因子发挥作用。我们已经表明，从晚期腺病毒感染细胞中纯化的SR蛋白（SR-Ad）通过病毒诱导的部分去磷酸化，作为剪接增强子或剪接抑制蛋白在功能上失活。在此，我们表明，从晚期痘苗病毒感染细胞中纯化的SR蛋白（SR-VV）也发生了低磷酸化，并且作为剪接调节蛋白在功能上失活。我们进一步表明，在使SR蛋白的磷酸表位得以恢复的条件下孵育SR-Ad蛋白，会使其作为剪接增强子和剪接抑制蛋白的活性得以恢复。有趣的是，SR-VV蛋白的重新磷酸化仅部分恢复了SR蛋白的剪接增强子或剪接抑制蛋白表型。总体而言，我们的结果表明，病毒对SR蛋白活性的控制可能是DNA病毒用来控制宿主细胞RNA剪接机制的一种常见策略。
