Secondary structure is the major determinant for interaction of HIV rev protein with RNA.
A region in the human immunodeficiency virus (HIV) env message, with the potential to form a complex secondary structure (designated RRE), interacts with the rev protein (Rev). This interaction is believed to mediate export of HIV structural messenger RNAs from the nucleus to the cytoplasm. In this report the regions essential for Rev interaction with the RRE are further characterized and the functional significance of Rev-RRE interaction in vivo is examined. A single hairpin loop structure within the RRE was found to be a primary determinant for Rev binding in vitro and Rev response in vivo. Maintenance of secondary structure, rather than primary nucleotide sequence alone, appeared to be necessary for Rev-RNA interaction, which distinguishes it from the mechanism for cis-acting elements in DNA. Limited changes within the 200 nucleotides, which preserved the proper RRE conformational structure, were well tolerated for Rev binding and function. Thus, variation among the RRE elements present in the diverse HIV isolates would have little, if any, effect on Rev responsiveness.
Department of Molecular Oncology and Virology, Roche Institute of Molecular Biology, Nutley, NJ 07110.
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Olsen
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Nelbock
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Cochrane
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Rosen
D001482:Base Composition; D001483:Base Sequence; D002872:Chromosome Deletion; D015694:Gene Products, rev / Q000235:genetics / Q000378:metabolism*; D015757:Genes, rev; D006678:HIV / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D010957:Plasmids; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D054321:rev Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D012333:RNA, Messenger; D012367:RNA, Viral; D015534:Trans-Activators; D054321:rev Gene Products, Human Immunodeficiency Virus