Cryo-EM structures of human RNA polymerase I.

Agata D Misiaszek, Mathias Girbig, Helga Grötsch, Florence Baudin, Brice Murciano, Aleix Lafita, Christoph W Müller

Nature structural & molecular biology 2021 Dec

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RNA polymerase I (Pol I) specifically synthesizes ribosomal RNA. Pol I upregulation is linked to cancer, while mutations in the Pol I machinery lead to developmental disorders. Here we report the cryo-EM structure of elongating human Pol I at 2.7 Å resolution. In the exit tunnel, we observe a double-stranded RNA helix that may support Pol I processivity. Our structure confirms that human Pol I consists of 13 subunits with only one subunit forming the Pol I stalk. Additionally, the structure of human Pol I in complex with the initiation factor RRN3 at 3.1 Å resolution reveals stalk flipping upon RRN3 binding. We also observe an inactivated state of human Pol I bound to an open DNA scaffold at 3.3 Å resolution. Lastly, the high-resolution structure of human Pol I allows mapping of disease-related mutations that can aid understanding of disease etiology. © 2021. The Author(s).

Citation

Agata D Misiaszek, Mathias Girbig, Helga Grötsch, Florence Baudin, Brice Murciano, Aleix Lafita, Christoph W Müller. Cryo-EM structures of human RNA polymerase I. Nature structural & molecular biology. 2021 Dec;28(12):997-1008