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.