RNA甲基化METTL3/METTL14/WTAP复合物激活剂可增加HIV复制。
HIV Replication Is Increased by RNA Methylation METTL3/METTL14/WTAP Complex Activators.
作者信息
Selberg Simona, Žusinaite Eva, Herodes Koit, Seli Neinar, Kankuri Esko, Merits Andres, Karelson Mati
机构信息
Institute of Chemistry, University of Tartu, Tartu 50411, Estonia.
Institute of Technology, University of Tartu, Tartu 50411, Estonia.
出版信息
ACS Omega. 2021 Jun 11;6(24):15957-15963. doi: 10.1021/acsomega.1c01626. eCollection 2021 Jun 22.
The N6-methyladenosine (mA) modifications in both viral and host cell RNAs play an important role in HIV-1 virus genome transcription and virus replication. We demonstrate here that activators of the METTL3/METTL14/WTAP RNA methyltransferase complex enhance the production of virus particles in cells harboring HIV-1 provirus. In parallel, the amount of mA residues in the host cell mRNA was increased in the presence of these activator compounds. Importantly, the mA methylation of the HIV-1 RNA was also enhanced significantly (about 18%). The increase of virus replication by the small-molecule activators of the METTL3/METTL14/WTAP complex excludes them as potential anti-HIV-1 drug candidates. However, the compounds may be of large interest as activators for the latent HIV-1 provirus copies deposited in host cells' genome and the subsequent virus eradication by an antiviral compound.
病毒RNA和宿主细胞RNA中的N6-甲基腺苷（m⁶A）修饰在HIV-1病毒基因组转录和病毒复制中发挥重要作用。我们在此证明，METTL3/METTL14/WTAP RNA甲基转移酶复合体的激活剂可增强携带HIV-1前病毒的细胞中病毒颗粒的产生。与此同时，在这些激活剂化合物存在的情况下，宿主细胞mRNA中m⁶A残基的数量增加。重要的是，HIV-1 RNA的m⁶A甲基化也显著增强（约18%）。METTL3/METTL14/WTAP复合体的小分子激活剂导致病毒复制增加，这排除了它们作为潜在抗HIV-1药物候选物的可能性。然而，这些化合物作为激活潜伏在宿主细胞基因组中的HIV-1前病毒拷贝以及随后通过抗病毒化合物根除病毒的激活剂，可能具有很大的研究价值。
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