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Cryo-EM structures of human RNA polymerase I.

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 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.

SUBMITTER: Misiaszek AD

PROVIDER: S-EPMC8660638 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Cryo-EM structures of human RNA polymerase I.

Misiaszek Agata D AD Girbig Mathias M Grötsch Helga H Baudin Florence F Murciano Brice B Lafita Aleix A Müller Christoph W CW

Nature structural & molecular biology 20211209 12

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 h ...[more]

PMID: 34887565

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