FTSJ3 is an RNA 2'-O-methyltransferase recruited by HIV to avoid innate immune sensing.
Nature
; 565(7740): 500-504, 2019 01.
Article
en En
| MEDLINE
| ID: mdl-30626973
ABSTRACT
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-ß 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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
VIH-1
/
Inmunidad Innata
/
Metiltransferasas
Límite:
Humans
Idioma:
En
Revista:
Nature
Año:
2019
Tipo del documento:
Article
País de afiliación:
Francia