The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans

Julia L Daiß, Michael Pilsl, Kristina Straub, Andrea Bleckmann, Mona Höcherl, Florian B Heiss, Guillermo Abascal-Palacios, Ewan P Ramsay, Katarina Tlučková, Jean-Clement Mars, Torben Fürtges, Astrid Bruckmann, Till Rudack, Carrie Bernecky, Valérie Lamour, Konstantin Panov, Alessandro Vannini, Tom Moss, Christoph Engel*

*Corresponding author for this work

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Transcription of the ribosomal RNA precursor by RNA polymerase (Pol) I is a major determinant of cellular growth, and dysregulation is observed in many cancer types. Here, we present the purification of human Pol I from cells carrying a genomic GFP fusion on the largest subunit allowing the structural and functional analysis of the enzyme across species. In contrast to yeast, human Pol I carries a single-subunit stalk, and in vitro transcription indicates a reduced proofreading activity. Determination of the human Pol I cryo-EM reconstruction in a close-to-native state rationalizes the effects of disease-associated mutations and uncovers an additional domain that is built into the sequence of Pol I subunit RPA1. This "dock II" domain resembles a truncated HMG box incapable of DNA binding which may serve as a downstream transcription factor-binding platform in metazoans. Biochemical analysis, in situ modelling, and ChIP data indicate that Topoisomerase 2a can be recruited to Pol I via the domain and cooperates with the HMG box domain-containing factor UBF. These adaptations of the metazoan Pol I transcription system may allow efficient release of positive DNA supercoils accumulating downstream of the transcription bubble.
Original languageEnglish
Article numbere202201568
JournalLife Science Alliance
Issue number11
Publication statusPublished - 01 Sep 2022


  • Animals
  • RNA Polymerase I - genetics - metabolism
  • DNA
  • Saccharomyces cerevisiae - metabolism
  • RNA Precursors
  • Transcription Factors - metabolism
  • Humans


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