Stimulation of RNA polymerase II elongation by hepatitis delta antigen

Transcription elongation by RNA polymerase II (RNAPII) is negatively regula ted by the human factors DRB-sensitivity inducing factor (DSIF) and negativ e elongation factor (NELF). A 66-kilodalton subunit of NELF (NELF-A) shows limited sequence similarity to hepatitis delta antigen (HDAg), the viral pr otein required for replication of hepatitis delta virus (HDV). The host RNA PII has been implicated in HDV replication, but the detailed mechanism and the role of HDAg in this process are not understood. We show that HDAg bind s RNAPII directly and stimulates transcription by displacing NELF and promo ting RNAPII elongation. These results suggest that HDAg may regulate RNAPII elongation during both cellular messenger RNA synthesis and HDV RNA replic ation.