[{"publication_status":"submitted","file_date_updated":"2023-12-05T10:37:02Z","has_accepted_license":"1","tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)"},"abstract":[{"lang":"eng","text":"Transcription by RNA polymerase II (Pol II) can be repressed by noncoding RNA, including the human RNA Alu. However, the mechanism by which endogenous RNAs repress transcription remains unclear. Here we present cryo-electron microscopy structures of Pol II bound to Alu RNA, which reveal that Alu RNA mimics how DNA and RNA bind to Pol II during transcription elongation. Further, we show how domains of the general transcription factor TFIIF affect complex dynamics and control repressive activity. Together, we reveal how a non-coding RNA can regulate mammalian gene expression."}],"ddc":["572"],"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"EM-Fac"},{"_id":"PreCl"}],"date_updated":"2023-12-05T10:37:28Z","_id":"14644","type":"preprint","date_created":"2023-12-04T14:51:00Z","doi":"10.15479/AT:ISTA:14644","author":[{"last_name":"Tluckova","full_name":"Tluckova, Katarina","id":"4AC7D980-F248-11E8-B48F-1D18A9856A87","first_name":"Katarina"},{"last_name":"Testa Salmazo","id":"41F1F098-F248-11E8-B48F-1D18A9856A87","full_name":"Testa Salmazo, Anita P","first_name":"Anita P"},{"orcid":"0000-0003-0893-7036","first_name":"Carrie A","id":"2CB9DFE2-F248-11E8-B48F-1D18A9856A87","full_name":"Bernecky, Carrie A","last_name":"Bernecky"}],"article_processing_charge":"No","day":"05","title":"Mechanism of mammalian transcriptional repression by noncoding RNA","oa_version":"Submitted Version","publisher":"Institute of Science and Technology Austria","citation":{"ista":"Tluckova K, Testa Salmazo AP, Bernecky C. Mechanism of mammalian transcriptional repression by noncoding RNA. <a href=\"https://doi.org/10.15479/AT:ISTA:14644\">10.15479/AT:ISTA:14644</a>.","chicago":"Tluckova, Katarina, Anita P Testa Salmazo, and Carrie Bernecky. “Mechanism of Mammalian Transcriptional Repression by Noncoding RNA.” Institute of Science and Technology Austria, n.d. <a href=\"https://doi.org/10.15479/AT:ISTA:14644\">https://doi.org/10.15479/AT:ISTA:14644</a>.","apa":"Tluckova, K., Testa Salmazo, A. P., &#38; Bernecky, C. (n.d.). Mechanism of mammalian transcriptional repression by noncoding RNA. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:14644\">https://doi.org/10.15479/AT:ISTA:14644</a>","mla":"Tluckova, Katarina, et al. <i>Mechanism of Mammalian Transcriptional Repression by Noncoding RNA</i>. Institute of Science and Technology Austria, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:14644\">10.15479/AT:ISTA:14644</a>.","ama":"Tluckova K, Testa Salmazo AP, Bernecky C. Mechanism of mammalian transcriptional repression by noncoding RNA. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:14644\">10.15479/AT:ISTA:14644</a>","ieee":"K. Tluckova, A. P. Testa Salmazo, and C. Bernecky, “Mechanism of mammalian transcriptional repression by noncoding RNA.” Institute of Science and Technology Austria.","short":"K. Tluckova, A.P. Testa Salmazo, C. Bernecky, (n.d.)."},"acknowledgement":"We thank B. Kaczmarek and other members of the Bernecky lab for helpful discussions. We thank V.-V. Hodirnau for SerialEM data collection and support with EPU data collection. We thank D. Slade for the wild type TFIIF expression\r\nplasmid. We thank N. Thompson and R. Burgess for the 8WG16 hybridoma cell line. We thank C. Plaschka and M. Loose for critical reading of the manuscript. This work was supported by Austrian Science Fund (FWF) grant P34185. This research was further supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Lab Support Facility (LSF), Electron Microscopy Facility (EMF), Scientific Computing (SciComp), and the Preclinical Facility (PCF).","date_published":"2023-12-05T00:00:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"project":[{"_id":"c08a6700-5a5b-11eb-8a69-82a722b2bc30","grant_number":"P34185","name":"Regulation of mammalian transcription by noncoding RNA"}],"language":[{"iso":"eng"}],"status":"public","department":[{"_id":"CaBe"}],"file":[{"checksum":"c45608cb97ee36d7b50ba518db8e07b0","relation":"main_file","access_level":"open_access","content_type":"application/pdf","success":1,"file_name":"2023_Tluckova_etal_REx.pdf","file_id":"14646","creator":"dernst","date_updated":"2023-12-05T10:37:02Z","date_created":"2023-12-05T10:37:02Z","file_size":4892920}],"year":"2023","month":"12"},{"article_number":"e202201568","file":[{"date_updated":"2022-09-08T06:41:14Z","creator":"dernst","date_created":"2022-09-08T06:41:14Z","file_size":3183129,"file_id":"12062","content_type":"application/pdf","access_level":"open_access","file_name":"2022_LifeScienceAlliance_Daiss.pdf","success":1,"checksum":"4201d876a3e5e8b65e319d03300014ad","relation":"main_file"}],"department":[{"_id":"CaBe"}],"month":"09","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"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>","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.","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.","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>","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>."},"issue":"11","language":[{"iso":"eng"}],"oa":1,"date_created":"2022-09-06T18:45:23Z","article_type":"original","volume":5,"oa_version":"Published Version","title":"The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans","day":"01","author":[{"first_name":"Julia L","full_name":"Daiß, Julia L","last_name":"Daiß"},{"first_name":"Michael","full_name":"Pilsl, Michael","last_name":"Pilsl"},{"full_name":"Straub, Kristina","last_name":"Straub","first_name":"Kristina"},{"first_name":"Andrea","full_name":"Bleckmann, Andrea","last_name":"Bleckmann"},{"last_name":"Höcherl","full_name":"Höcherl, Mona","first_name":"Mona"},{"first_name":"Florian B","last_name":"Heiss","full_name":"Heiss, Florian B"},{"first_name":"Guillermo","last_name":"Abascal-Palacios","full_name":"Abascal-Palacios, Guillermo"},{"last_name":"Ramsay","full_name":"Ramsay, Ewan P","first_name":"Ewan P"},{"last_name":"Tluckova","full_name":"Tluckova, Katarina","id":"4AC7D980-F248-11E8-B48F-1D18A9856A87","first_name":"Katarina"},{"last_name":"Mars","full_name":"Mars, Jean-Clement","first_name":"Jean-Clement"},{"full_name":"Fürtges, Torben","last_name":"Fürtges","first_name":"Torben"},{"first_name":"Astrid","last_name":"Bruckmann","full_name":"Bruckmann, Astrid"},{"full_name":"Rudack, Till","last_name":"Rudack","first_name":"Till"},{"first_name":"Carrie A","orcid":"0000-0003-0893-7036","id":"2CB9DFE2-F248-11E8-B48F-1D18A9856A87","full_name":"Bernecky, Carrie A","last_name":"Bernecky"},{"first_name":"Valérie","full_name":"Lamour, Valérie","last_name":"Lamour"},{"first_name":"Konstantin","last_name":"Panov","full_name":"Panov, Konstantin"},{"full_name":"Vannini, Alessandro","last_name":"Vannini","first_name":"Alessandro"},{"last_name":"Moss","full_name":"Moss, Tom","first_name":"Tom"},{"first_name":"Christoph","full_name":"Engel, Christoph","last_name":"Engel"}],"file_date_updated":"2022-09-08T06:41:14Z","publication_status":"published","publication_identifier":{"issn":["2575-1077"]},"abstract":[{"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.","lang":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"intvolume":"         5","has_accepted_license":"1","keyword":["Health","Toxicology and Mutagenesis","Plant Science","Biochemistry","Genetics and Molecular Biology (miscellaneous)","Ecology"],"external_id":{"isi":["000972702600001"]},"year":"2022","isi":1,"date_published":"2022-09-01T00:00:00Z","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).","status":"public","publication":"Life Science Alliance","type":"journal_article","_id":"12051","date_updated":"2023-08-03T13:39:36Z","publisher":"Life Science Alliance","article_processing_charge":"No","doi":"10.26508/lsa.202201568","quality_controlled":"1","ddc":["570"]}]