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The landscape of SARS-CoV-2 RNA modifications

View ORCID ProfileMilad Miladi, Jonas Fuchs, View ORCID ProfileWolfgang Maier, View ORCID ProfileSebastian Weigang, Núria Díaz i Pedrosa, Lisa Weiss, View ORCID ProfileAchim Lother, View ORCID ProfileAnton Nekrutenko, View ORCID ProfileZsolt Ruzsics, View ORCID ProfileMarcus Panning, View ORCID ProfileGeorg Kochs, View ORCID ProfileRalf Gilsbach, View ORCID ProfileBjörn Grüning
doi: https://doi.org/10.1101/2020.07.18.204362
Milad Miladi
1Department of Computer Science, University of Freiburg, Freibug, Germany
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Jonas Fuchs
2Institute of Virology, University Medical Center Freiburg, Freiburg, Germany
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Wolfgang Maier
1Department of Computer Science, University of Freiburg, Freibug, Germany
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Sebastian Weigang
2Institute of Virology, University Medical Center Freiburg, Freiburg, Germany
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Núria Díaz i Pedrosa
3German Center for Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt am Main, Germany
4Institute for Cardiovascular Physiology, Medical Faculty, Goethe University Frankfurt am Main, Frankfurt am Main, Germany
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Lisa Weiss
3German Center for Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt am Main, Germany
4Institute for Cardiovascular Physiology, Medical Faculty, Goethe University Frankfurt am Main, Frankfurt am Main, Germany
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Achim Lother
5Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, Freiburg, Germany
6Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Anton Nekrutenko
7Huck Institutes of the Life Sciences and the Department of Biochemistry and Molecular Biology, Penn State University, Pennsylvania, USA
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Zsolt Ruzsics
2Institute of Virology, University Medical Center Freiburg, Freiburg, Germany
8Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Marcus Panning
2Institute of Virology, University Medical Center Freiburg, Freiburg, Germany
8Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Georg Kochs
2Institute of Virology, University Medical Center Freiburg, Freiburg, Germany
8Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Ralf Gilsbach
3German Center for Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt am Main, Germany
4Institute for Cardiovascular Physiology, Medical Faculty, Goethe University Frankfurt am Main, Frankfurt am Main, Germany
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  • For correspondence: gilsbach@vrc.uni-frankfurt.de gruening@informatik.uni-freiburg.de
Björn Grüning
1Department of Computer Science, University of Freiburg, Freibug, Germany
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  • For correspondence: gilsbach@vrc.uni-frankfurt.de gruening@informatik.uni-freiburg.de
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Abstract

In 2019 the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the first documented cases of severe lung disease COVID-19. Since then, SARS-CoV-2 has been spreading around the globe resulting in a severe pandemic with over 500.000 fatalities and large economical and social disruptions in human societies. Gaining knowledge on how SARS-Cov-2 interacts with its host cells and causes COVID-19 is crucial for the intervention of novel therapeutic strategies. SARS-CoV-2, like other coronaviruses, is a positive-strand RNA virus. The viral RNA is modified by RNA-modifying enzymes provided by the host cell. Direct RNA sequencing (DRS) using nanopores enables unbiased sensing of canonical and modified RNA bases of the viral transcripts. In this work, we used DRS to precisely annotate the open reading frames and the landscape of SARS-CoV-2 RNA modifications. We provide the first DRS data of SARS-CoV-2 in infected human lung epithelial cells. From sequencing three isolates, we derive a robust identification of SARS-CoV-2 modification sites within a physiologically relevant host cell type. A comparison of our data with the DRS data from a previous SARS-CoV-2 isolate, both raised in monkey renal cells, reveals consistent RNA modifications across the viral genome. Conservation of the RNA modification pattern during progression of the current pandemic suggests that this pattern is likely essential for the life cycle of SARS-CoV-2 and represents a possible target for drug interventions.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://covid19.galaxyproject.org

  • https://bit.ly/usegalaxy-eu-covid19-data

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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The landscape of SARS-CoV-2 RNA modifications
Milad Miladi, Jonas Fuchs, Wolfgang Maier, Sebastian Weigang, Núria Díaz i Pedrosa, Lisa Weiss, Achim Lother, Anton Nekrutenko, Zsolt Ruzsics, Marcus Panning, Georg Kochs, Ralf Gilsbach, Björn Grüning
bioRxiv 2020.07.18.204362; doi: https://doi.org/10.1101/2020.07.18.204362
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The landscape of SARS-CoV-2 RNA modifications
Milad Miladi, Jonas Fuchs, Wolfgang Maier, Sebastian Weigang, Núria Díaz i Pedrosa, Lisa Weiss, Achim Lother, Anton Nekrutenko, Zsolt Ruzsics, Marcus Panning, Georg Kochs, Ralf Gilsbach, Björn Grüning
bioRxiv 2020.07.18.204362; doi: https://doi.org/10.1101/2020.07.18.204362

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