RNA polymerase II (RNA Pol II) subunits are thought to be involved in various transcription-associated processes, 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 functions. We found that RNA Pol II subunits contribute differently to RNA Pol II cellular localization and transcription processes and preferentially regulate RNA processing (such as RNA splicing and 3′ end maturation). Genes sensitive to the depletion of different RNA Pol II subunits tend to be involved in diverse biological functions 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.

RNA 聚合酶 II (RNA Pol II) 亚基被认为参与各种转录相关过程，但尚不清楚它们是否在调节基因表达中发挥不同的调节作用。在这里，我们在 12 个哺乳动物 RNA Pol II 亚基急性降解后进行了新生和成熟的转录本测序，并分析了它们的基因组结合位点和蛋白质相互作用组，以剖析它们的分子功能。我们发现 RNA Pol II 亚基对 RNA Pol II 细胞定位和转录过程的贡献不同，并优先调节 RNA 加工（如 RNA 剪接和 3' 端成熟）。对不同 RNA Pol II 亚基耗尽敏感的基因往往参与不同的生物学功能，并表现出不同的 RNA 半衰期。序列，相关的蛋白质因子，和 RNA 结构与 RNA Pol II 亚基介导的差异基因表达相关。这些发现共同表明，RNA Pol II 和不同基因的异质性似乎取决于某些亚基。