{"article_type":"original","title":"The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans","issue":"11","license":"https://creativecommons.org/licenses/by/4.0/","quality_controlled":"1","external_id":{"isi":["000972702600001"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","doi":"10.26508/lsa.202201568","publication":"Life Science Alliance","_id":"12051","article_number":"e202201568","language":[{"iso":"eng"}],"publication_identifier":{"issn":["2575-1077"]},"keyword":["Health","Toxicology and Mutagenesis","Plant Science","Biochemistry","Genetics and Molecular Biology (miscellaneous)","Ecology"],"oa":1,"abstract":[{"lang":"eng","text":"Transcription of the ribosomal RNA precursor by RNA polymerase (Pol) I is a major determinant of cellular growth, and dysregulation is observed in many cancer types. Here, we present the purification of human Pol I from cells carrying a genomic GFP fusion on the largest subunit allowing the structural and functional analysis of the enzyme across species. In contrast to yeast, human Pol I carries a single-subunit stalk, and in vitro transcription indicates a reduced proofreading activity. Determination of the human Pol I cryo-EM reconstruction in a close-to-native state rationalizes the effects of disease-associated mutations and uncovers an additional domain that is built into the sequence of Pol I subunit RPA1. This “dock II” domain resembles a truncated HMG box incapable of DNA binding which may serve as a downstream transcription factor–binding platform in metazoans. Biochemical analysis, in situ modelling, and ChIP data indicate that Topoisomerase 2a can be recruited to Pol I via the domain and cooperates with the HMG box domain–containing factor UBF. These adaptations of the metazoan Pol I transcription system may allow efficient release of positive DNA supercoils accumulating downstream of the transcription bubble."}],"tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2022-09-01T00:00:00Z","publication_status":"published","month":"09","date_updated":"2023-08-03T13:39:36Z","ddc":["570"],"file":[{"file_name":"2022_LifeScienceAlliance_Daiss.pdf","file_id":"12062","creator":"dernst","date_created":"2022-09-08T06:41:14Z","relation":"main_file","checksum":"4201d876a3e5e8b65e319d03300014ad","date_updated":"2022-09-08T06:41:14Z","access_level":"open_access","success":1,"content_type":"application/pdf","file_size":3183129}],"publisher":"Life Science Alliance","volume":5,"day":"01","oa_version":"Published Version","file_date_updated":"2022-09-08T06:41:14Z","intvolume":"         5","acknowledgement":"The authors especially thank Philip Gunkel for his contribution. We thank all\r\npast and present members of the Engel lab, Achim Griesenbeck, Colyn Crane-\r\nRobinson, Christophe Lotz, Marlene Vayssieres, Klaus Grasser, Herbert Tschochner, and Philipp Milkereit for help and discussion; Gerhard Lehmann and Nobert Eichner for IT support; Joost Zomerdijk for UBF-constructs, Volker Cordes for the Hela P2 cell line; Remco Sprangers for shared cell culture; Dina Grohmann and the Archaea Center for fermentation; and Thomas\r\nDresselhaus for access to fluorescence microscopes. This work was in part supported by the Emmy-Noether Programm (DFG grant no. EN 1204/1-1 to C Engel) of the German Research Council and Collaborative Research Center 960 (TP-A8 to C Engel).","date_created":"2022-09-06T18:45:23Z","year":"2022","type":"journal_article","citation":{"apa":"Daiß, J. L., Pilsl, M., Straub, K., Bleckmann, A., Höcherl, M., Heiss, F. B., … Engel, C. (2022). The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans. <i>Life Science Alliance</i>. Life Science Alliance. <a href=\"https://doi.org/10.26508/lsa.202201568\">https://doi.org/10.26508/lsa.202201568</a>","short":"J.L. Daiß, M. Pilsl, K. Straub, A. Bleckmann, M. Höcherl, F.B. Heiss, G. Abascal-Palacios, E.P. Ramsay, K. Tluckova, J.-C. Mars, T. Fürtges, A. Bruckmann, T. Rudack, C. Bernecky, V. Lamour, K. Panov, A. Vannini, T. Moss, C. Engel, Life Science Alliance 5 (2022).","chicago":"Daiß, Julia L, Michael Pilsl, Kristina Straub, Andrea Bleckmann, Mona Höcherl, Florian B Heiss, Guillermo Abascal-Palacios, et al. “The Human RNA Polymerase I Structure Reveals an HMG-like Docking Domain Specific to Metazoans.” <i>Life Science Alliance</i>. Life Science Alliance, 2022. <a href=\"https://doi.org/10.26508/lsa.202201568\">https://doi.org/10.26508/lsa.202201568</a>.","ista":"Daiß JL, Pilsl M, Straub K, Bleckmann A, Höcherl M, Heiss FB, Abascal-Palacios G, Ramsay EP, Tluckova K, Mars J-C, Fürtges T, Bruckmann A, Rudack T, Bernecky C, Lamour V, Panov K, Vannini A, Moss T, Engel C. 2022. The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans. Life Science Alliance. 5(11), e202201568.","mla":"Daiß, Julia L., et al. “The Human RNA Polymerase I Structure Reveals an HMG-like Docking Domain Specific to Metazoans.” <i>Life Science Alliance</i>, vol. 5, no. 11, e202201568, Life Science Alliance, 2022, doi:<a href=\"https://doi.org/10.26508/lsa.202201568\">10.26508/lsa.202201568</a>.","ieee":"J. L. Daiß <i>et al.</i>, “The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans,” <i>Life Science Alliance</i>, vol. 5, no. 11. Life Science Alliance, 2022.","ama":"Daiß JL, Pilsl M, Straub K, et al. The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans. <i>Life Science Alliance</i>. 2022;5(11). doi:<a href=\"https://doi.org/10.26508/lsa.202201568\">10.26508/lsa.202201568</a>"},"author":[{"full_name":"Daiß, Julia L","last_name":"Daiß","first_name":"Julia L"},{"first_name":"Michael","last_name":"Pilsl","full_name":"Pilsl, Michael"},{"full_name":"Straub, Kristina","last_name":"Straub","first_name":"Kristina"},{"first_name":"Andrea","full_name":"Bleckmann, Andrea","last_name":"Bleckmann"},{"first_name":"Mona","full_name":"Höcherl, Mona","last_name":"Höcherl"},{"first_name":"Florian B","last_name":"Heiss","full_name":"Heiss, Florian B"},{"full_name":"Abascal-Palacios, Guillermo","last_name":"Abascal-Palacios","first_name":"Guillermo"},{"last_name":"Ramsay","full_name":"Ramsay, Ewan P","first_name":"Ewan P"},{"first_name":"Katarina","last_name":"Tluckova","full_name":"Tluckova, Katarina","id":"4AC7D980-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jean-Clement","full_name":"Mars, Jean-Clement","last_name":"Mars"},{"first_name":"Torben","full_name":"Fürtges, Torben","last_name":"Fürtges"},{"first_name":"Astrid","last_name":"Bruckmann","full_name":"Bruckmann, Astrid"},{"full_name":"Rudack, Till","last_name":"Rudack","first_name":"Till"},{"last_name":"Bernecky","orcid":"0000-0003-0893-7036","id":"2CB9DFE2-F248-11E8-B48F-1D18A9856A87","full_name":"Bernecky, Carrie A","first_name":"Carrie A"},{"full_name":"Lamour, Valérie","last_name":"Lamour","first_name":"Valérie"},{"full_name":"Panov, Konstantin","last_name":"Panov","first_name":"Konstantin"},{"full_name":"Vannini, Alessandro","last_name":"Vannini","first_name":"Alessandro"},{"first_name":"Tom","full_name":"Moss, Tom","last_name":"Moss"},{"first_name":"Christoph","full_name":"Engel, Christoph","last_name":"Engel"}],"status":"public","department":[{"_id":"CaBe"}],"isi":1,"has_accepted_license":"1","article_processing_charge":"No"}