The Hepatitis B Virus Posttranscriptional Regulatory Element Contains a Highly Stable RNA Secondary Structure

Hepatitis B virus (HBV) transcripts contain a sequence known as the posttranscriptional regulatory element (PRE). This element was shown to facilitate the nuclear export of the S gene transcripts, to partially substitute for the human immunodeficiency virus (HIV-1) Rev-response element (RRE), and to bind two cellular factors. Within the genetically defined PRE (approximately 450 nucleotides), we identified a highly stable secondary structural element of 313 nucleotides in length termed PRE313. The energy values of the PRE313 are similar to those of the RRE of HIV-1 and significantly lower than those of other portions of HBV RNA. A comparison of human HBV subtypes shows strong conservation of the PRE313 in terms of energy and structure, providing further evidence for the biological significance of the genetically defined PRE and the PRE313 in particular. The structural model for the PRE313 described in this study may help in identifying crucial components of the transport mechanism of transcripts of HBV.