Targeted protein degradation reveals RNA Pol II heterogeneity and functional diversity

Abstract

RNA polymerase II (RNA Pol II) subunits are thought to be involved in various transcription-associated pro-cesses, but it is unclear whether they play different regulatory roles in modulating gene expression. Here, we performed nascent and mature transcript sequencing after the acute degradation of 12 mammalian RNA Pol II subunits and profiled their genomic binding sites and protein interactomes to dissect their molecular func-tions. We found that RNA Pol II subunits contribute differently to RNA Pol II cellular localization and transcrip-tion processes and preferentially regulate RNA processing (such as RNA splicing and 30 end maturation). Genes sensitive to the depletion of different RNA Pol II subunits tend to be involved in diverse biological func-tions and show different RNA half-lives. Sequences, associated protein factors, and RNA structures are correlated with RNA Pol II subunit-mediated differential gene expression. These findings collectively suggest that the heterogeneity of RNA Pol II and different genes appear to depend on some of the subunits.