Predicted secondary structure of a minimal functional RRE (sequence from HXB3 strain) with the major stem loops labeled. In the cytoplasm, these messages are translated to produce the remaining viral proteins or packaged as genomes for newly budding virions ( Fig. 1A) (for a detailed review, see ref. Nuclear export of such RNAs is achieved by a specific, cooperative assembly of multiple Rev molecules on the RRE, followed by recruitment of the host Crm1/Ran-GTP nuclear export machinery via Rev’s nuclear export sequence (NES). Normally, these intron-containing RNAs are retained in the nucleus for splicing/degradation. The late phase of the viral life cycle is characterized by the expression of viral proteins from RRE-containing unspliced (9 kb) and partially spliced (4 kb) messages. (B) Genome organization of HIV-1: The RRE lies between nucleotides 7709–8063. In the late phase, intronic, RRE-containing RNAs in the nucleus recruit Rev and cellular nuclear-export machinery to circumvent splicing and reach the cytoplasm where they are translated or packaged into new virions. A subset of these transcripts codes for Rev, which is imported into the nucleus. (A) Functional requirement of the RRE: Early in the viral life cycle, all viral transcripts are fully spliced and exported in a Rev/RRE-independent manner.
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