Abstract
Human Hepatitis B Virus (HBV) RNAs contain a cis-acting sequence, the post-transcriptional regulatory element (HPRE), which facilitates the cytoplasmic localization of intronless transcripts. Our previous studies have shown that the HPRE is composed of at least two independent sub-elements, HPREα and HPREβ, which co-activate a reporter for RNA export in a greater than additive manner. Utilizing deletion, mutation and co-variational analyses, we have identified three regions important for full HPRE activity. The three separate regions of the HPRE function can function independently in a dose-dependent manner when multimerized. Two of these regions contain stem loops, HSLα and HSLβ1, which are necessary for full HPRE function. These structures are conserved throughout the mammalian Hepadnaviruses. Disruption of either stem-loop structure by mutagenesis decreases HPRE function while compensatory mutations restore activity. The location of the stem-loops in the genome reveal that they are present in all of the HBV transcripts. HSLα and HSLβ1 are likely to contain the binding sites for the cellular factor(s) which mediates HPRE function.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4818-4827 |
| Number of pages | 10 |
| Journal | Nucleic acids research |
| Volume | 26 |
| Issue number | 21 |
| DOIs | |
| State | Published - Nov 1 1998 |
Funding
We are grateful to Lydia N. Drumright for technical assistance and Leslie Barden and Allison Bocksruker for secretarial assistance. We would like to thank Matthew Harris and Matthew Weissman for critical reading of the manuscript. G.J.S. is supported by the Chapman Charitable Trust. J.E.D. is supported by NCI training grant T32 CA64041. T.J.H. is supported by the ARATA Brothers Trust and the Gene and Ruth Posner Foundation. This study was supported by National Institutes of Health grant AI35477 to T.J.H and grants from the Deutsche Forschungsgemeinschaft (Ste 465/3).
ASJC Scopus subject areas
- Genetics
