近日，德国马克斯普朗克多学科科学研究所Patrick Cramer及其团队开发出流感聚合酶共转录夺帽机制。该研究于2026年3月4日发表于国际一流学术期刊《自然》杂志上。

在这里，该研究组展示了低温电子显微镜下的结构与转录Pol II配合物与延伸因子DSIF在裂解前状态。该结构表明，FluPol直接与Pol II和DSIF相互作用，将FluPol内切酶结构域定位在Pol II的RNA出口通道附近。这些相互作用对于FluPol的内切酶活性和细胞中的FluPol活性是重要的。第二种结构，在夺帽后被捕获，表明被切割的带帽RNA在FluPol内重新排列，将带帽RNA的3'端指向FluPol聚合酶活性位点，以启动病毒转录。总之，他们的研究结果提供了FluPol共转录夺帽的分子机制。

据了解，流感病毒mRNA是稳定的，能够进行核输出和转译，因为它们在一个称为夺帽的过程中获得了一个5' cap(1)结构。在夺帽过程中，病毒RNA依赖的RNA聚合酶（FluPol）与宿主RNA聚合酶II （Pol II）和新出现的转录结合。然后，FluPol内切酶切割一个带帽的RNA片段，该片段随后作为病毒基因转录的引物。

附：英文原文

Title: Mechanism of co-transcriptional cap snatching by influenza polymerase

Author: Rotsch, Alexander Helmut, Li, Delong, Dupont, Maud, Krischuns, Tim, Neef, Ute, Oberthr, Christiane, Stelfox, Alice, Lukarska, Maria, Fianu, Isaac, Lidschreiber, Michael, Naffakh, Nadia, Dienemann, Christian, Cusack, Stephen, Cramer, Patrick

Issue&Volume: 2026-03-04

Abstract: Influenza virus mRNAs are stable and competent for nuclear export and translation because they receive a 5′ cap(1) structure in a process called cap snatching1. During cap snatching, the viral RNA-dependent RNA polymerase (FluPol) binds to host RNA polymerase II (Pol II) and the emerging transcript2,3. The FluPol endonuclease then cleaves a capped RNA fragment that subsequently acts as a primer for the transcription of viral genes4,5. Here we present the cryogenic electron microscopy structure of FluPol bound to a transcribing Pol II in complex with the elongation factor DSIF in the pre-cleavage state. The structure shows that FluPol directly interacts with both Pol II and DSIF, positioning the FluPol endonuclease domain near the RNA exit channel of Pol II. These interactions are important for the endonuclease activity of FluPol and FluPol activity in cells. A second structure, trapped after cap snatching, shows that the cleaved capped RNA rearranges within FluPol, directing the capped RNA 3′ end toward the FluPol polymerase active site for viral transcription initiation. Together, our results provide the molecular mechanisms of co-transcriptional cap snatching by FluPol.

DOI: 10.1038/s41586-026-10189-0

Source: https://www.nature.com/articles/s41586-026-10189-0