Hepatitis B virus S transcripts contain a region, known as the posttranscriptional regulatory element (PRE), that activates their transport from the nucleus to the cytoplasm. J. Huang and T. J. Liang (Mol. Cell. Biol. 13:7476-7486, 1993) have shown that this element can partially substitute for the human immunodeficiency virus Rev-response element (RRE) in a reporter plasmid that is dependent on the RRE and Rev protein for expression and concluded that PRE exhibits Rev-RRE-like functions by inhibiting splicing. However, we have obtained additional data which indicate that the PRE functions in a novel manner that is not dependent on inhibition of splicing. Unlike Rev-RRE, the PRE functions independently of splice donor and acceptor sites and can activate cytoplasmic expression of an intronless (so-called prespliced) beta-globin transcript. Conversely, a heterologous intron can substitute for the PRE in increasing cytoplasmic expression of hepatitis B virus S transcripts. In addition, the host nuclear factor, YL2 (p32), which enhances Rev-RRE function has no effect on PRE-dependent gene expression. Since S transcripts are not normally known to be spliced and since RNA splicing and cytoplasmic transport are tightly linked processes in higher eucaryotic cells, we conclude that the PRE functions in cis to allow the export of nuclear transcripts that do not interact efficiently with the splicing pathway and hence are normally not exported well from the nucleus. Such elements are critical for the life cycle of viruses, such as hepatitis B virus, which undergo reverse transcription during replication.
Woodchuck Hepatitis Virus Contains a Tripartite Posttranscriptional Regulatory Element