RNA polymerase II holoenzyme stability determines the number of base pairs that can be transcribed before the holoenzyme loses its ability to transcribe. The length of the CTD is essential for RNA polymerase II stability. RNA polymerase II stability has been shown to be regulated by post-translation proline hydroxylation. The von Hippel–Lindau tumor suppressor protein (pVHL, human GeneID: 7428) complex binds the hyperphosphorylated large subunit of the RNA polymerase II complex, in a proline hydroxylation- and CTD phosphorylation-dependent manner, targeting it for ubiquitination.