mRNA,疱疹病毒 z-bo 2020-10-22 455

　　In the long-term game between the virus and the host, various mechanisms have been developed to counteract and circumvent the host’s antiviral response. One of the key strategies is to prevent the establishment of host cells by intervening in the process of exporting host mRNA to the nucleus. Appropriate anti-viral environment. For example, it has been shown that the NS1 protein of influenza A virus and the M protein of follicular stomatitis virus can broadly inhibit the export of host mRNA from the nucleus. In a 2016 study, some ORF10 proteins encoded by gamma herpes viruses (such as Kaposi's sarcoma-associated virus KSHV and mouse gamma herpes virus MHV68) interacted with the host mRNA transport complex Rae1-Nup98. Found that it can specifically inhibit. Nuclear transport of host mRNA. ORF10 is the first toxic protein found in herpes viruses that can prevent host mRNA from being transported from the nucleus, and it is also the first reported viral protein that can selectively prevent the transport of specific mRNA. However, the structural basis of the complex interaction between ORF10 and Rae1-Nup98 and the molecular mechanism of ORF10's inhibitory function are still unknown.

　　On October 8, the Gaopu research group of the Institute of Biophysics of the Chinese Academy of Sciences cooperated with Deng Hongyu's research group to selectively inhibit mRNA nuclear export through the herpes virus protein ORF10 on PNAS. I published a research paper entitled "Mechanism". This research uses biochemistry, structural biology and cell biology techniques. Analyze the details of the interaction between the γ-herpesvirus ORF10 and the host mRNA transport complex Rae1-Nup98, confirm the RNA binding ability of ORF10 and its important functions, and ORF10 selectively inhibits the transport of mRNA from the nucleus.

　　Did the researchers use the insect cell expression system to prepare samples of the ORF10-Rae1-Nup98 ternary complex in good condition and analyze the complex 2.5? Resolve crystal structure. Structural analysis shows that there are two main interaction interfaces between ORF10 and Rae1-Nup98 complex. In these two interaction interfaces, the two highly conserved amino acids L60 and M413 of ORF10 contribute to important hydrophobic interactions. L60 and M413 interact between ORF10 and Rae1-Nup98 through Co-IP, in vitro pull-down, GFP reporter gene expression measurement, GFP-mRNA nuclear and cytoplasmic distribution measurement, RNAFISH imaging, and other biochemical cell experiments. Obviously, we are maintaining it. It is very important to maintain the output suppression function of ORF10 mRNA.