2008年3月，中科院生物物理所高光侠课题组再次于美国《国家科学院院刊》（PNAS）发表文章，题名为：“ZAP的抗病毒功能依赖于RNA解旋酶p72”。
宿主在与病毒长期共存的过程中进化出多种抗病毒机制，包括表达宿主限制性因子抑制病毒的复制。锌指抗病毒蛋白（Zinc-finger Antiviral Protein, ZAP）是一种重要的抗病毒因子，ZAP能通过降解特异病毒RNA进而抑制包括鼠白血病病毒在内的多种病毒的复制。
文章中作者发现，ZAP功能的正常发挥有赖于RNA解旋酶p72。ZAP与p72之间存在不依赖RNA的直接相互作用；过量表达p72能够促进ZAP的功能；通过RNAi的方法抑制内源表达的p72或者过量表达p72的C端,ZAP降解RNA的活性则受到抑制。进一步研究发现，p72存在于ZAP与核酸外切酶复合体形成的大的复合体之中。ZAP 抗病毒机制的研究不仅可能为病毒的防治提供新的策略和技术手段，也将有助于我们更深入了解RNA 稳定性的调控机理。
该成果受到了国家自然科学基金、科技部973计划和院知识创新工程的资助。（来源：中科院生物物理研究所）
生物谷推荐原始出处：
（PNAS），vol. 105 | no. 11 | 4352-4357，Guifang Chen, Guangxia Gao
p72 DEAD box RNA helicase is required for optimal function of the zinc-finger antiviral protein
Guifang Chen, Xuemin Guo, Fengxiang Lv, Yihui Xu, and Guangxia Gao*
Center for Infections and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Communicated by Stephen P. Goff, Columbia University, New York, NY, December 30, 2007 (received for review December 4, 2007)
The zinc-finger antiviral protein (ZAP) specifically inhibits the replication of many viruses by preventing the accumulation of viral mRNAs in the cytoplasm. ZAP directly binds to the viral mRNAs and recruits the RNA exosome to degrade the target RNA. In the present study, we identified the p72 DEAD box RNA helicase, but not the highly similar RNA helicase p68, as a ZAP-interacting protein. The binding domain of ZAP was mapped to its N-terminal portion, whereas both the N- and C-terminal domains of p72 bound to ZAP. Overexpression of the C-terminal domain of p72 reduced ZAP's activity, whereas overexpression of the full-length p72 enhanced ZAP's activity. The RNA helicase activity was required for p72 to promote ZAP-mediated RNA degradation. Depletion of p72 by RNAi also reduced ZAP's activity but did not affect tristetraprolin-mediated RNA degradation. We conclude that p72 is required for the optimal activity of ZAP, and we propose that p72 helps to restructure the ZAP-bound target mRNA for efficient degradation.
