[{"date_created":"2024-01-04T08:23:01Z","publisher":"Oxford University Press (OUP)","title":"Plant mitochondrial RNA editing factors can perform targeted C-to-U editing of nuclear transcripts in human cells","issue":"17","year":"2022","language":[{"iso":"eng"}],"keyword":["Genetics"],"publication":"Nucleic Acids Research","abstract":[{"text":"<jats:title>Abstract</jats:title>\r\n               <jats:p>RNA editing processes are strikingly different in animals and plants. Up to thousands of specific cytidines are converted into uridines in plant chloroplasts and mitochondria whereas up to millions of adenosines are converted into inosines in animal nucleo-cytosolic RNAs. It is unknown whether these two different RNA editing machineries are mutually incompatible. RNA-binding pentatricopeptide repeat (PPR) proteins are the key factors of plant organelle cytidine-to-uridine RNA editing. The complete absence of PPR mediated editing of cytosolic RNAs might be due to a yet unknown barrier that prevents its activity in the cytosol. Here, we transferred two plant mitochondrial PPR-type editing factors into human cell lines to explore whether they could operate in the nucleo-cytosolic environment. PPR56 and PPR65 not only faithfully edited their native, co-transcribed targets but also different sets of off-targets in the human background transcriptome. More than 900 of such off-targets with editing efficiencies up to 91%, largely explained by known PPR-RNA binding properties, were identified for PPR56. Engineering two crucial amino acid positions in its PPR array led to predictable shifts in target recognition. We conclude that plant PPR editing factors can operate in the entirely different genetic environment of the human nucleo-cytosol and can be intentionally re-engineered towards new targets.</jats:p>","lang":"eng"}],"volume":50,"author":[{"last_name":"Lesch","full_name":"Lesch, Elena","first_name":"Elena"},{"first_name":"Maximilian T","full_name":"Schilling, Maximilian T","last_name":"Schilling"},{"last_name":"Brenner","full_name":"Brenner, Sarah","first_name":"Sarah"},{"full_name":"Yang, Yingying","last_name":"Yang","first_name":"Yingying"},{"first_name":"Oliver J","full_name":"Gruss, Oliver J","last_name":"Gruss"},{"last_name":"Knoop","full_name":"Knoop, Volker","first_name":"Volker"},{"first_name":"Mareike","full_name":"Schallenberg-Rüdinger, Mareike","last_name":"Schallenberg-Rüdinger"}],"date_updated":"2024-01-04T08:23:13Z","doi":"10.1093/nar/gkac752","publication_identifier":{"issn":["0305-1048","1362-4962"]},"publication_status":"published","page":"9966-9983","intvolume":"        50","citation":{"ama":"Lesch E, Schilling MT, Brenner S, et al. Plant mitochondrial RNA editing factors can perform targeted C-to-U editing of nuclear transcripts in human cells. <i>Nucleic Acids Research</i>. 2022;50(17):9966-9983. doi:<a href=\"https://doi.org/10.1093/nar/gkac752\">10.1093/nar/gkac752</a>","ieee":"E. Lesch <i>et al.</i>, “Plant mitochondrial RNA editing factors can perform targeted C-to-U editing of nuclear transcripts in human cells,” <i>Nucleic Acids Research</i>, vol. 50, no. 17, pp. 9966–9983, 2022, doi: <a href=\"https://doi.org/10.1093/nar/gkac752\">10.1093/nar/gkac752</a>.","chicago":"Lesch, Elena, Maximilian T Schilling, Sarah Brenner, Yingying Yang, Oliver J Gruss, Volker Knoop, and Mareike Schallenberg-Rüdinger. “Plant Mitochondrial RNA Editing Factors Can Perform Targeted C-to-U Editing of Nuclear Transcripts in Human Cells.” <i>Nucleic Acids Research</i> 50, no. 17 (2022): 9966–83. <a href=\"https://doi.org/10.1093/nar/gkac752\">https://doi.org/10.1093/nar/gkac752</a>.","short":"E. Lesch, M.T. Schilling, S. Brenner, Y. Yang, O.J. Gruss, V. Knoop, M. Schallenberg-Rüdinger, Nucleic Acids Research 50 (2022) 9966–9983.","bibtex":"@article{Lesch_Schilling_Brenner_Yang_Gruss_Knoop_Schallenberg-Rüdinger_2022, title={Plant mitochondrial RNA editing factors can perform targeted C-to-U editing of nuclear transcripts in human cells}, volume={50}, DOI={<a href=\"https://doi.org/10.1093/nar/gkac752\">10.1093/nar/gkac752</a>}, number={17}, journal={Nucleic Acids Research}, publisher={Oxford University Press (OUP)}, author={Lesch, Elena and Schilling, Maximilian T and Brenner, Sarah and Yang, Yingying and Gruss, Oliver J and Knoop, Volker and Schallenberg-Rüdinger, Mareike}, year={2022}, pages={9966–9983} }","mla":"Lesch, Elena, et al. “Plant Mitochondrial RNA Editing Factors Can Perform Targeted C-to-U Editing of Nuclear Transcripts in Human Cells.” <i>Nucleic Acids Research</i>, vol. 50, no. 17, Oxford University Press (OUP), 2022, pp. 9966–83, doi:<a href=\"https://doi.org/10.1093/nar/gkac752\">10.1093/nar/gkac752</a>.","apa":"Lesch, E., Schilling, M. T., Brenner, S., Yang, Y., Gruss, O. J., Knoop, V., &#38; Schallenberg-Rüdinger, M. (2022). Plant mitochondrial RNA editing factors can perform targeted C-to-U editing of nuclear transcripts in human cells. <i>Nucleic Acids Research</i>, <i>50</i>(17), 9966–9983. <a href=\"https://doi.org/10.1093/nar/gkac752\">https://doi.org/10.1093/nar/gkac752</a>"},"department":[{"_id":"27"}],"user_id":"67287","_id":"50149","project":[{"name":"PC2: Computing Resources Provided by the Paderborn Center for Parallel Computing","_id":"52"}],"type":"journal_article","status":"public"},{"publication_identifier":{"issn":["0305-1048","1362-4962"]},"publication_status":"published","year":"2021","page":"3048-3062","intvolume":"        49","citation":{"ama":"Ijäs H, Shen B, Heuer-Jungemann A, et al. Unraveling the interaction between doxorubicin and DNA origami nanostructures for customizable chemotherapeutic drug release. <i>Nucleic Acids Research</i>. 2021;49:3048-3062. doi:<a href=\"https://doi.org/10.1093/nar/gkab097\">10.1093/nar/gkab097</a>","ieee":"H. Ijäs <i>et al.</i>, “Unraveling the interaction between doxorubicin and DNA origami nanostructures for customizable chemotherapeutic drug release,” <i>Nucleic Acids Research</i>, vol. 49, pp. 3048–3062, 2021.","chicago":"Ijäs, Heini, Boxuan Shen, Amelie Heuer-Jungemann, Adrian Keller, Mauri A Kostiainen, Tim Liedl, Janne A Ihalainen, and Veikko Linko. “Unraveling the Interaction between Doxorubicin and DNA Origami Nanostructures for Customizable Chemotherapeutic Drug Release.” <i>Nucleic Acids Research</i> 49 (2021): 3048–62. <a href=\"https://doi.org/10.1093/nar/gkab097\">https://doi.org/10.1093/nar/gkab097</a>.","apa":"Ijäs, H., Shen, B., Heuer-Jungemann, A., Keller, A., Kostiainen, M. A., Liedl, T., … Linko, V. (2021). Unraveling the interaction between doxorubicin and DNA origami nanostructures for customizable chemotherapeutic drug release. <i>Nucleic Acids Research</i>, <i>49</i>, 3048–3062. <a href=\"https://doi.org/10.1093/nar/gkab097\">https://doi.org/10.1093/nar/gkab097</a>","short":"H. Ijäs, B. Shen, A. Heuer-Jungemann, A. Keller, M.A. Kostiainen, T. Liedl, J.A. Ihalainen, V. Linko, Nucleic Acids Research 49 (2021) 3048–3062.","mla":"Ijäs, Heini, et al. “Unraveling the Interaction between Doxorubicin and DNA Origami Nanostructures for Customizable Chemotherapeutic Drug Release.” <i>Nucleic Acids Research</i>, vol. 49, 2021, pp. 3048–62, doi:<a href=\"https://doi.org/10.1093/nar/gkab097\">10.1093/nar/gkab097</a>.","bibtex":"@article{Ijäs_Shen_Heuer-Jungemann_Keller_Kostiainen_Liedl_Ihalainen_Linko_2021, title={Unraveling the interaction between doxorubicin and DNA origami nanostructures for customizable chemotherapeutic drug release}, volume={49}, DOI={<a href=\"https://doi.org/10.1093/nar/gkab097\">10.1093/nar/gkab097</a>}, journal={Nucleic Acids Research}, author={Ijäs, Heini and Shen, Boxuan and Heuer-Jungemann, Amelie and Keller, Adrian and Kostiainen, Mauri A and Liedl, Tim and Ihalainen, Janne A and Linko, Veikko}, year={2021}, pages={3048–3062} }"},"date_updated":"2022-01-06T06:55:37Z","volume":49,"author":[{"first_name":"Heini","last_name":"Ijäs","full_name":"Ijäs, Heini"},{"full_name":"Shen, Boxuan","last_name":"Shen","first_name":"Boxuan"},{"first_name":"Amelie","last_name":"Heuer-Jungemann","full_name":"Heuer-Jungemann, Amelie"},{"first_name":"Adrian","orcid":"0000-0001-7139-3110","last_name":"Keller","full_name":"Keller, Adrian","id":"48864"},{"full_name":"Kostiainen, Mauri A","last_name":"Kostiainen","first_name":"Mauri A"},{"full_name":"Liedl, Tim","last_name":"Liedl","first_name":"Tim"},{"last_name":"Ihalainen","full_name":"Ihalainen, Janne A","first_name":"Janne A"},{"full_name":"Linko, Veikko","last_name":"Linko","first_name":"Veikko"}],"date_created":"2021-07-08T11:46:53Z","title":"Unraveling the interaction between doxorubicin and DNA origami nanostructures for customizable chemotherapeutic drug release","doi":"10.1093/nar/gkab097","publication":"Nucleic Acids Research","type":"journal_article","abstract":[{"text":"<jats:title>Abstract</jats:title>\r\n               <jats:p>Doxorubicin (DOX) is a common drug in cancer chemotherapy, and its high DNA-binding affinity can be harnessed in preparing DOX-loaded DNA nanostructures for targeted delivery and therapeutics. Although DOX has been widely studied, the existing literature of DOX-loaded DNA-carriers remains limited and incoherent. Here, based on an in-depth spectroscopic analysis, we characterize and optimize the DOX loading into different 2D and 3D scaffolded DNA origami nanostructures (DONs). In our experimental conditions, all DONs show similar DOX binding capacities (one DOX molecule per two to three base pairs), and the binding equilibrium is reached within seconds, remarkably faster than previously acknowledged. To characterize drug release profiles, DON degradation and DOX release from the complexes upon DNase I digestion was studied. For the employed DONs, the relative doses (DOX molecules released per unit time) may vary by two orders of magnitude depending on the DON superstructure. In addition, we identify DOX aggregation mechanisms and spectral changes linked to pH, magnesium, and DOX concentration. These features have been largely ignored in experimenting with DNA nanostructures, but are probably the major sources of the incoherence of the experimental results so far. Therefore, we believe this work can act as a guide to tailoring the release profiles and developing better drug delivery systems based on DNA-carriers.</jats:p>","lang":"eng"}],"status":"public","_id":"22637","department":[{"_id":"302"}],"user_id":"48864","language":[{"iso":"eng"}]}]