The RNA polymerase II general transcription factor TFIIB is a target for transcriptome control during cellular stress and viral infection

Abstract

AbstractMany stressors, including viral infection, induce a widespread suppression of cellular RNA polymerase II (RNAPII) transcription, yet the mechanisms underlying transcriptional repression are not well understood. Here we find that a crucial component of the RNA polymerase II holoenzyme, general transcription factor IIB (TFIIB), is targeted for post-translational turnover by two pathways, each of which contribute to its depletion during stress. Upon DNA damage, translational stress, apoptosis, or lytic infection with the oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV), TFIIB is cleaved by activated caspase-3, leading to preferential downregulation of pro-survival genes. TFIIB is further targeted for rapid proteasome-mediated turnover by the E3 ubiquitin ligase TRIM28. KSHV counteracts proteasome-mediated turnover of TFIIB, thereby preserving a sufficient pool of TFIIB for transcription of viral genes. Thus, TFIIB may be a lynchpin for transcriptional outcomes during stress and a key target for nuclear replicating DNA viruses that rely on host transcriptional machinery.Graphical Abstract