Ricardo SOTO-RIFO, Institute of Biomedical Sciences - Universidad de Chile

The HIV-1 genomic RNA (gRNA) plays two major roles in the cytoplasm of infected cells serving as the mRNA for the synthesis of the structural proteins Gag and Gag-Pol but also as the genome packaged into newly produced viral particles. However, the mechanism allowing the discrimination between these two functions has remained elusive for several years. It was recently reported that the HIV-1 gRNA contains N6-methyladenosine (m6A), which was proposed to play a positive role in viral gene expression. We provide evidence for a negative role of m6A in HIV-1 genomic RNA packaging. As such, we identified two adenosine residues located within the 5´-untranslated region as the key residues involved in this regulation. Interestingly, we observed that the Gag protein associates with the RNA demethylase FTO and drives demethylation of the HIV-1 gRNA to promote packaging. We finally demonstrate that this epitranscrioptmic regulation can be targeted pharmacologically using a specific inhibitor of the FTO RNA demethylase activity. 
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Dr. Soto-Rifo studied biochemistry at Universidad de Santiago de Chile and then moved to Lyon, France where he obtained a Master in Sciences degree from Université Claude Bernard Lyon-1 in 2006 and then a Ph.D in Life Sciences from Ecole Normale Supérieure de Lyon in 2010. He worked at the Human Virology Department (currently the International Center for Infectiology Research) under the supervision of Dr. Théophile Ohlmann on the translational control of the HIV-1 and HIV-2 genomic RNA. During his post-doctoral training at Dr. Ohlmann`s lab, Dr. Soto-Rifo worked on the remodeling and localization of the messenger ribonucleoprotein complexes (mRNPs) containing the HIV-1 genomic RNA by analyzing the role of the DEAD-box RNA helicase DDX3 in these processes. In 2013, he moved to the Biomedical Sciences Institute at Universidad de Chile Faculty of Medicine to start his own laboratory at the Viriology Program. Since, Dr. Soto-Rifo has established his research group, which is mainly focused in understand the mechanisms involved in RNA metabolism during HIV-1, HIV-2, respiratory syncytial virus and Zika virus replication.

The talk will be focused on the role of the RNA modification N6-methyladenosine (m6A) and its associated cellular machinery in defining the cytoplasmic destiny of the HIV-1 genomic RNA during the late steps of the viral replication cycle.

Contact : E. Ricci