Cryo-EM structures of human RNA polymerase I

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 angstrom 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 angstrom 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 angstrom resolution. Lastly, the high-resolution structure of human Pol I allows mapping of disease-related mutations that can aid understanding of disease etiology. Here the authors structurally investigate elongating human RNA polymerase I at 2.7 angstrom using cryo-electron microscopy, as well as an RNA polymerase I open complex at 3.3 angstrom and bound to initiation factor RRN3 at 3.2 angstrom.

Automated summary

The study investigates the elongating human RNA polymerase I structure at 2.7 angstrom, as well as an RNA polymerase I open complex at 3.3 angstrom and bound to initiation factor RRN3 at 3.2 angstrom using cryo-electron microscopy.