Cryo-EM structures of human RNA polymerase I

Misiaszek, A. D.; Girbig, M.; Grötsch, H.; Baudin, F.; Lafita, A.; Murciano, B.; Müller, C. W.

doi:10.1101/2021.05.31.446457

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bioRxiv · 10.1101/2021.05.31.446457

Cryo-EM structures of human RNA polymerase I

Misiaszek, A. D.·Girbig, M.·Grötsch, H.·Baudin, F.·Lafita, A.·Murciano, B.·Müller, C. W.

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Abstract

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 [A] 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 [A] 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 [A] resolution. Lastly, the high-resolution structure of human Pol I allows mapping of disease-related mutations that can aid understanding of disease etiology.

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Misiaszek, A. D., Girbig, M., Grötsch, H., Baudin, F., Lafita, A., Murciano, B., Müller, C. W.. 2021-06-01. Cryo-EM structures of human RNA polymerase I. https://doi.org/10.1101/2021.05.31.446457

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