Modification of small hepatitis delta virus antigen by SUMO protein.
Hepatitis delta antigen (HDAg) is a nuclear protein that is intimately involved in hepatitis delta virus (HDV) RNA replication. HDAg consists of two protein species, the small form (S-HDAg) and the large form (L-HDAg). Previous studies have shown that posttranslational modifications of S-HDAg, such as phosphorylation, acetylation, and methylation, can modulate HDV RNA replication. In this study, we show that S-HDAg is a small ubiquitin-like modifier 1 (SUMO1) target protein. Mapping data showed that multiple lysine residues are SUMO1 acceptors within S-HDAg. Using a genetic fusion strategy, we found that conjugation of SUMO1 to S-HDAg selectively enhanced HDV genomic RNA and mRNA synthesis but not antigenomic RNA synthesis. This result supports our previous proposition that the cellular machinery involved in the synthesis of HDV antigenomic RNA is different from that for genomic RNA synthesis and mRNA transcription, requiring different modified forms of S-HDAg. Sumoylation represents a new type of modification for HDAg.
Tseng
Chung-Hsin
CH
Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
Cheng
Tai-Shan
TS
Shu
Chiung-Yueh
CY
Jeng
King-Song
KS
Lai
Michael M C
MM
D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D016679:Genome, Viral; D003698:Hepatitis Delta Virus / Q000235:genetics / Q000378:metabolism*; D035923:Hepatitis delta Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques
D035923:Hepatitis delta Antigens; D012333:RNA, Messenger; D012367:RNA, Viral; D025842:SUMO-1 Protein