Cellular proteins that bind to the hepatitis B virus posttranscriptional regulatory element

The hepatitis B virus posttranscriptional regulatory element (PRE), which resides in the 3' region of the viral S transcripts, is important for the high-level expression of these mRNA species. We have previously shown that the PRE acts intranuclearly in cis to allow efficient export of intronless transcripts into the cytoplasm, in a manner that is independent of viral trans-acting factors. We here present data demonstrating that there are widely dispersed subelements in the PRE that are important for its function. All of these subelements bind, albeit with different affinities, to the same or similar host nuclear factor(s) containing two proteins, approximately 30 and 45 kDa in mass. The affinity of protein binding to a subelement is positively correlated with the ability of the subelement to activate intronless gene expression. Therefore, it appears that the PRE functions by having multiple binding sites for nuclear proteins that may be directly or indirectly involved in export of unspliced mRNA species.