Background The HIV-1 genomic RNA (gRNA) has several roles in the viral life cycle. In the nucleus, the gRNA is the pre-mRNA that is alternatively and incompletely spliced into mRNAs encoding Tat, Rev, Nef, Vif, Vpr, Vpu and Env. However, approximately 50% of the gRNA remains unspliced and is exported from the nucleus by the viral protein Rev using the CRM1 nuclear export pathway. In the cytoplasm, the gRNA serves as the mRNA for Gag and Gag-Pol and is also packaged into virions. As the gRNA is an unspliced, intron-containing mRNA with a long, highly structured 5’ UTR and rare codon usage in the open reading frames, how it interacts with cellular RNA metabolism and translation machinery to promote abundant Gag expression and infectious virion production remains unclear.