Solution structure of stem-loop alpha of the hepatitis B virus post-transcriptional regulatory element.
Chronic hepatitis B virus (HBV) infections may lead to severe diseases like liver cirrhosis or hepatocellular carcinoma (HCC). The HBV post-transcriptional regulatory element (HPRE) facilitates the nuclear export of unspliced viral mRNAs, contains a splicing regulatory element and resides in the 3'-region of all viral transcripts. The HPRE consists of three sub-elements alpha (nucleotides 1151-1346), beta1 (nucleotides 1347-1457) and beta2 (nucleotides 1458-1582), which confer together full export competence. Here, we present the NMR solution structure (pdb 2JYM) of the stem-loop alpha (SLalpha, nucleotides 1292-1321) located in the sub-element alpha. The SLalpha contains a CAGGC pentaloop highly conserved in hepatoviruses, which essentially adopts a CUNG-like tetraloop conformation. Furthermore, the SLalpha harbours a single bulged G residue flanked by A-helical regions. The structure is highly suggestive of serving two functions in the context of export of unspliced viral RNA: binding sterile alpha motif (SAM-) domain containing proteins and/or preventing the utilization of a 3'-splice site contained within SLalpha.
Schwalbe
Martin
M
Leibniz-Institut für Altersforschung/Fritz-Lipmann-Institut, Beutenbergstr. 11, D-07745 Jena, Germany.
Ohlenschläger
Oliver
O
Marchanka
Aliaksandr
A
Ramachandran
Ramadurai
R
Häfner
Sabine
S
Heise
Tilman
T
Görlach
Matthias
M
D006515:Hepatitis B virus / Q000235:genetics*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D034443:RNA Transport; D012367:RNA, Viral / Q000737:chemistry* / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid; D012996:Solutions
D012367:RNA, Viral; D038621:Regulatory Sequences, Ribonucleic Acid; D012996:Solutions