NF-κB Binds P-TEFb to Stimulate Transcriptional Elongation by RNA Polymerase II

Abstract

To stimulate transcriptional elongation of HIV-1 genes, the transactivator Tat recruits the positive transcription elongation factor b (P-TEFb) to the initiating RNA polymerase II (RNAPII). We found that the activation of transcription by RelA also depends on P-TEFb. Similar to Tat, RelA activated transcription when tethered to RNA. Moreover, TNF-α triggered the recruitment of P-TEFb to the NF-κB-regulated IL-8 gene. While the formation of the transcription preinitiation complex (PIC) remained unaffected, DRB, an inhibitor of P-TEFb, prevented RNAPII from elongating on the IL-8 gene. Remarkably, DRB inhibition sensitized cells to TNF-α-induced apoptosis. Thus, NF-κB requires P-TEFb to stimulate the elongation of transcription and P-TEFb plays an unexpected role in regulating apoptosis.