FTSJ3 is an RNA 2 '-O-methyltransferase recruited by HIV to avoid innate immune sensing

Article

关键词: MESSENGER-RNA;    BINDING PROTEIN;    RESTRICTION;    METHYLATION;    SAMHD1;    SELF;    TRBP;   

DOI  :  10.1038/s41586-018-0841-4

来源: SCIE

【 摘 要 】

In mammals, 2'-O-methylation of RNA is a molecular signature by which the cellular innate immune system distinguishes endogenous from exogenous messenger RNA1-3. However, the molecular functions of RNA 2'-O-methylation are not well understood. Here we have purified TAR RNA-binding protein (TRBP) and its interacting partners and identified a DICER-independent TRBP complex containing FTSJ3, a putative 2'-O-methyltransferase (2' O-MTase). In vitro and ex vivo experiments show that FTSJ3 is a 2' O-MTase that is recruited to HIV RNA through TRBP. Using RiboMethSeq analysis4, we identified predominantly FTSJ3-dependent 2'-O-methylations at specific residues on the viral genome. HIV-1 viruses produced in FTSJ3 knockdown cells show reduced 2'-O-methylation and trigger expression of type 1 interferons (IFNs) in human dendritic cells through the RNA sensor MDA5. This induction of IFN-a and IFN-beta leads to a reduction in HIV expression. We have identified an unexpected mechanism used by HIV-1 to evade innate immune recognition: the recruitment of the TRBP-FTSJ3 complex to viral RNA and its 2'-O-methylation.

【 授权许可】

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