8A43

Human RNA polymerase I

Summary for 8A43

• Entry DOI: 10.2210/pdb8a43/pdb
• EMDB information: 15135
• Descriptor: DNA-directed RNA polymerase I subunit RPA1, DNA-directed RNA polymerases I, II, and III subunit RPABC4, DNA-directed RNA polymerase I subunit RPA49, ... (12 entities in total)
• Functional Keywords: rna polymerase i, human rdna transcription, transcription
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 565233.50

Authors

Daiss, J.L.,Pilsl, M.,Straub, K.,Bleckmann, A.,Hoecherl, M.,Heiss, F.B.,Abascal-Palacios, G.,Ramsay, E.,Tluckova, K.,Mars, J.C.,Fuertges, T.,Bruckmann, A.,Rudack, T.,Bernecky, C.,Lamour, V.,Panov, K.,Vannini, A.,Moss, T.,Engel, C. (deposition date: 2022-06-10, release date: 2022-08-31, Last modification date: 2024-11-20)

Primary citation

Daiss, J.L.,Pilsl, M.,Straub, K.,Bleckmann, A.,Hocherl, M.,Heiss, F.B.,Abascal-Palacios, G.,Ramsay, E.P.,Tluckova, K.,Mars, J.C.,Furtges, T.,Bruckmann, A.,Rudack, T.,Bernecky, C.,Lamour, V.,Panov, K.,Vannini, A.,Moss, T.,Engel, C.
The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans.
Life Sci Alliance, 5:-, 2022

PubMed Abstract: 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.

PubMed: 36271492
DOI: 10.26508/lsa.202201568

Experimental method

ELECTRON MICROSCOPY (4.09 Å)