Late human immunodeficiency virus (HIV)-derived RNAs encoding relevant therapeutic targets or promising vaccine compounds, such as the HIV-1 group-specific antigen (Gag), are translocated from the nucleus into the cytoplasm via sophisticated export machinery. Relevant steps include the concerted action of several cis-acting RNA elements with the viral Rev-shuttle protein and several cellular components (Ran1/Exportin; Crm1). Based on detailed understanding of the molecular mechanisms guiding this complex process, we used rational codon usage modification to design and reprogram a GFP encoding reporter RNA now exactly mimicking the complex transcriptional and posttranscriptional regulation of late lentiviral mRNAs.