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 Å resolution. In the exit tunnel, we observe a double...

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Autores principales: Misiaszek, Agata D., Girbig, Mathias, Grötsch, Helga, Baudin, Florence, Murciano, Brice, Lafita, Aleix, Müller, Christoph W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660638/
https://www.ncbi.nlm.nih.gov/pubmed/34887565
http://dx.doi.org/10.1038/s41594-021-00693-4
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author Misiaszek, Agata D.
Girbig, Mathias
Grötsch, Helga
Baudin, Florence
Murciano, Brice
Lafita, Aleix
Müller, Christoph W.
author_facet Misiaszek, Agata D.
Girbig, Mathias
Grötsch, Helga
Baudin, Florence
Murciano, Brice
Lafita, Aleix
Müller, Christoph W.
author_sort Misiaszek, Agata D.
collection PubMed
description 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.
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spelling pubmed-86606382021-12-27 Cryo-EM structures of human RNA polymerase I Misiaszek, Agata D. Girbig, Mathias Grötsch, Helga Baudin, Florence Murciano, Brice Lafita, Aleix Müller, Christoph W. Nat Struct Mol Biol Article 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. Nature Publishing Group US 2021-12-09 2021 /pmc/articles/PMC8660638/ /pubmed/34887565 http://dx.doi.org/10.1038/s41594-021-00693-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Misiaszek, Agata D.
Girbig, Mathias
Grötsch, Helga
Baudin, Florence
Murciano, Brice
Lafita, Aleix
Müller, Christoph W.
Cryo-EM structures of human RNA polymerase I
title Cryo-EM structures of human RNA polymerase I
title_full Cryo-EM structures of human RNA polymerase I
title_fullStr Cryo-EM structures of human RNA polymerase I
title_full_unstemmed Cryo-EM structures of human RNA polymerase I
title_short Cryo-EM structures of human RNA polymerase I
title_sort cryo-em structures of human rna polymerase i
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660638/
https://www.ncbi.nlm.nih.gov/pubmed/34887565
http://dx.doi.org/10.1038/s41594-021-00693-4
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