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Nature. 2019 Jan;565(7740):500-504. doi: 10.1038/s41586-018-0841-4. Epub 2019 Jan 9.

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

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IGH, CNRS, Université de Montpellier, Montpellier, France.
Next-Generation Sequencing Core Facility, UMS2008 IBSLor CNRS-University of Lorraine-INSERM, BioPole, Vandoeuvre-les-Nancy, France.
CNRS, Aix-Marseille University, AFMB, Marseille, France.
IMoPA UMR7365 CNRS-University of Lorraine, BioPole, Vandoeuvre-les-Nancy, France.
IGH, CNRS, Université de Montpellier, Montpellier, France.


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-α and IFN-β 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.


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