Methylation of Delta Antigen

S-HDAg was shown to be methylated in vitro and in vivo (Li et al. 2004). The major methylation site is at arginine 13 (R13) in the RGGR motif of S-HDAg. The methylation of S-HDAg is crucial for HDV RNA replication, especially for replication of the genomic RNA from the antigenomic RNA. A substitution at R13 of S-HDAg, or treatment with methylation inhibitors, reduced HDV RNA replication. The methylation status of S-HDAg affected its subcellular localization. Both the R13A mutant of S-HDAg, and wild-type S-HDAg in cells treated with a methylation inhibitor, were localized mainly in the cytoplasm, whereas wild-type S-HDAg formed speckled structures in the nucleus. Furthermore, the methylation of S-HDAg is involved in the transportation of antigenomic RNA, but not genomic RNA. Moreover, when introduced as a ribonucleoprotein (RNP) complex, antigenomic RNA, but not genomic RNA, failed to be targeted to the nucleus with unmethylated S-HDAg. These results indicate that methylation of S-HDAg plays an important role in the replication of HDV RNA and methylated HDAg is required for the initiation of replication of genomic RNA from the antigenomic strand.

0 0

Post a comment