Role of cytoplasmic N6-methyladenosine (m6A) readers on HIV-2 protein synthesis
Fecha
20182018
Institución
Resumen
N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNA and has been involved
in the post-transcriptional regulation of gene expression. The effects of this modification are mainly exerted by the
recruitment of any of the m6A reader proteins YTHDF1, 2 and 3 or YTHDC1 and YTHDC2 to the methylated mRNA.
m6A has also been reported in several viral RNA including that of HIV-1, HCV, ZIKV, amongst others. In the case
of HIV-1, it was reported that DF proteins binds the unspliced mRNA to promote Gag synthesis. In this work, we
have investigated the role of m6A readers in HIV-2 protein synthesis and the subcellular localization of the unspliced
mRNA. Our results indicate that, in contrast to what was reported for HIV-1, overexpression of DF proteins exerts
different effects on HIV-2 protein synthesis. As such, while overexpression of YTHDF1 and 2 promotes Gag and Vpx
synthesis, overexpression of YTHDF3 negatively regulates this process. Interestingly, we observed that DF proteins
relocalize together with the HIV-2 gRNA to stress granules, sites where the viral genome is stored in the absence of
active translation. Together, these data show that HIV-2 protein synthesis is differentially regulated by DF proteins
and that these m6A readers associates with the HIV-2 unspliced mRNA and are relocalized to stress granules during
viral replication. HIV-2 is less pathogenic and replicates at very low rates when compared to HIV-1. We are currently
investigating whether these features of HIV-2 are regulated at the epitranscriptomic level.
Fondecyt grant N° 1160176 to RSR—Conicyt fellowship folio N° 221160818 to SR