Degradation of DNA damage-independently stalled RNA polymerase II is independent of the E3 ligase Elc1

Transcription elongation is a highly dynamic and dis-continuous process, which includes frequent paus-ing of RNA polymerase II (RNAPII). RNAPII com-plexes that stall persistently on a gene during tran-scription elongation block transcription and thus have to be removed. It has been proposed that the cellular pathway for removal of these DNA damage-independently stalled RNAPII complexes is similar or identical to the removal of RNAPII complexes stalled due to DNA damage. Here, we show that––consistent with previous data––DNA damage-independent stalling causes polyubiquityla-tion and proteasome-mediated degradation of Rpb1, the largest subunit of RNAPII, using Saccharomyces cerevisiae as model system. Moreover, recruitment of the proteasome to RNAPII and transcribed genes is increased when transcription elongation is im-paired indicating that Rpb1 degradation takes place at the gene. Importantly, in contrast to the DNA damage-dependent pathway Rpb1 degradation of DNA damage-independently stalled RNAPII is inde-pendent of the E3 ligase Elc1. In addition, deubiqui-tylation of RNAPII is also independent of the Elc1-antagonizing deubiquitylase Ubp3. Thus, the path-way for degradation of DNA damage-independently stalled RNAPII is overlapping yet distinct from the previously described pathway for degradation of RNAPII stalled due to DNA damage. Taken together, we provide the first evidence that the cell dis-criminates between DNA damage-dependently and-independently stalled RNAPII