Transcription start site choice regulates HIV-1 RNA conformation and function

HIV-1, the causative agent of AIDS, is a retrovirus that packages two copies of unspliced viral RNA as a dimer into newly budding virions. The unspliced viral RNA also serves as an mRNA template for translation of two polyproteins. Recent studies suggest that the fate of the viral RNA (genome or mRNA) is determined at the level of transcription. RNA polymerase II uses heterogeneous transcription start sites to generate major transcripts that differ in only two guanosines at the 5' end. Remarkably, this two-nucleotide difference is sufficient to alter the structure of the 5'-untranslated region and generate two pools of RNA with distinct functions. The presence of both RNA species is needed for optimal viral replication and fitness.