Three highly conserved, multisubunit RNA polymerase (RNAP) enzymes, RNAPs I, II, and III, transcribe the eukaryotic nuclear genome (reviewed by Cramer et al. 2008, Vannini and Cramer 2012, Griesenbeck et al. 2017, Cramer 2019). Each one synthesizes different classes of RNA from DNA templates: RNAP I synthesizes the ribosomal RNA precursor that is processed into most ribosomal RNAs (rRNAs), RNAP II makes messenger RNAs (mRNAs) and a variety of non-coding RNAs, and RNAP III synthesizes short, non-coding RNAs including transfer RNAs (tRNAs), the small 5S rRNA and the U6 small nuclear RNA. Each RNAP contains between 12–17 subunits, ten of which form a structurally conserved catalytic core with additional subunits located on the periphery. Notably, five subunits are shared among all three RNAPs and two others are shared between RNAPs I and III. In contrast to the nuclear RNAPs, a single subunit mitochondrial RNAP transcribes the rRNAs, mRNAs and tRNAs of the mitochondrial genome (Arnold et al. 2012).