ROLE OF THE HEPATITIS-B VIRUS POSTTRANSCRIPTIONAL REGULATORY ELEMENT IN EXPORT OF INTRONLESS TRANSCRIPTS

Hepatitis B virus S transcripts contain a region, known as the posttra nscriptional regulatory element (PRE), that activates their transport from the nucleus to the cytoplasm. J. Huang and T. J. Liang (Mel. 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 prote in for expression and concluded that PRE exhibits Rev-RRE-like functio ns by inhibiting splicing. However, we have obtained additional data w hich indicate that the PRE functions in a novel manner that is not dep endent on inhibition of splicing. Unlike Rev-RRE, the PRE functions in dependently of splice donor and acceptor sites and can activate cytopl asmic expression of an intronless (so called prespliced) beta-globin t ranscript. Conversely, a heterologous intron can substitute for the PR E in increasing cytoplasmic expression of hepatitis B virus S transcri pts. In addition, the host nuclear factor, YL2 (p32), which enhances R ev-RRE function has no effect on PRE-dependent gene expression, Since S transcripts are not normally known to be spliced and since RNA splic ing and cytoplasmic transport are tightly linked processes in higher e ucaryotic cells, we conclude that the PRE functions in cis to allow th e 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, su ch as hepatitis B virus, which undergo reverse transcription during re plication.