title: The HIV-1 Rev response element (RRE) adopts alternative conformations that promote different rates of virus replication.
abstract: The HIV Rev protein forms a complex with a 351 nucleotide sequence present in unspliced and incompletely spliced human immunodeficiency virus (HIV) mRNAs, the Rev response element (RRE), to recruit the cellular nuclear export receptor Crm1 and Ran-GTP. This complex facilitates nucleo-cytoplasmic export of these mRNAs. The precise secondary structure of the HIV-1 RRE has been controversial, since studies have reported alternative structures comprising either four or five stem-loops. The published structures differ only in regions that lie outside of the primary Rev binding site. Using in-gel SHAPE, we have now determined that the wt NL4-3 RRE exists as a mixture of both structures. To assess functional differences between these RRE 'conformers', we created conformationally locked mutants by site-directed mutagenesis. Using subgenomic reporters, as well as HIV replication assays, we demonstrate that the five stem-loop form of the RRE promotes greater functional Rev/RRE activity compared to the four stem-loop counterpart.
authors: Myles H. Thaler Center for AIDS and Human Retrovirus Research, Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA.
authors: Chringma
authors: C
authors: Sherpa
authors: Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD 21702, USA.
authors: Jason W
authors: JW
authors: Rausch
authors: Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD 21702, USA.
authors: Stuart F J
authors: SF
authors: Le Grice
authors: Myles H. Thaler Center for AIDS and Human Retrovirus Research, Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA mh7g@virginia.edu.
authors: Marie-Louise
authors: ML
authors: Hammarskjold
authors: Myles H. Thaler Center for AIDS and Human Retrovirus Research, Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA dr4u@virginia.edu.
authors: David
authors: D
authors: Rekosh
mesh_terms: D015685:Fusion Proteins, gag-pol / Q000378:metabolism; D015752:Genes, env; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D009154:Mutation; D009690:Nucleic Acid Conformation; D012367:RNA, Viral / Q000737:chemistry* / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid; D014779:Virus Replication / Q000235:genetics*; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D015685:Fusion Proteins, gag-pol; D012367:RNA, Viral; D038621:Regulatory Sequences, Ribonucleic Acid; D054321:rev Gene Products, Human Immunodeficiency Virus; C514860:rev protein, Human Immunodeficiency Virus-1