Dynamics of HIV-1 Rev sub-nuclear trafficking reveal new insight into the role of RNA in the regulation of Rev nucleolar accumulation

Background The Nucleolus is a sub-nuclear compartment controlling key cellular processes, including ribosome biogenesis, transcriptional regulation, RNA trafficking and cell cycle control. Nucleolar structure is maintained through accumulation and release of retained proteins, which are selectively immobilised by RNA-protein, and/or proteinprotein interactions. As part of their replicative strategy, viruses can target the nucleolus. Specifically, the essential HIV-1 regulatory protein, Rev, selectively hijacks the Importin b/ Transportin and CRM-1 transport pathways in order to shuttle between the nucleolus and the cytoplasm, facilitating the nuclear export of singly and unspliced HIV-1 mRNA. In this context, the nucleolar trafficking of HIV-1 Rev and viral transcripts could be crucial in controlling HIV-1 gene expression & replication. However, the nature of this association remains to be investigated in living cells. To better understand the molecular determinants of Rev nucleolar accumulation, we monitored HIV-1 Rev intra-nuclear movements in real time & under distinct physiological conditions using photo-convertible Dendra2 (Evrogen), and compared it the nucleolar trafficking of HIV-1 Tat, the orchestrator of HIV-1 transcription.