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The architecture of SARS-CoV-2 transcriptome

Dongwan Kim, Joo-Yeon Lee, Jeong-Sun Yang, Jun Won Kim, View ORCID ProfileV. Narry Kim, View ORCID ProfileHyeshik Chang
doi: https://doi.org/10.1101/2020.03.12.988865
Dongwan Kim
1Center for RNA Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea
2School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea
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Joo-Yeon Lee
3Korea National Institute of Health, Korea Centers for Disease Control & Prevention, Osong 28159, Republic of Korea
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Jeong-Sun Yang
3Korea National Institute of Health, Korea Centers for Disease Control & Prevention, Osong 28159, Republic of Korea
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Jun Won Kim
3Korea National Institute of Health, Korea Centers for Disease Control & Prevention, Osong 28159, Republic of Korea
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V. Narry Kim
1Center for RNA Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea
2School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea
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  • For correspondence: narrykim@snu.ac.kr hyeshik@snu.ac.kr
Hyeshik Chang
1Center for RNA Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea
2School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea
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  • ORCID record for Hyeshik Chang
  • For correspondence: narrykim@snu.ac.kr hyeshik@snu.ac.kr
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Summary

SARS-CoV-2 is a betacoronavirus that is responsible for the COVID-19 pandemic. The genome of SARS-CoV-2 was reported recently, but its transcriptomic architecture is unknown. Utilizing two complementary sequencing techniques, we here present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous recombination events, both canonical and noncanonical. In addition to the genomic RNA and subgenomic RNAs common in all coronaviruses, SARS-CoV-2 produces a large number of transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif being AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the internal modification and the 3′ tail. Functional investigation of the unknown ORFs and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2.

Highlights

  • We provide a high-resolution map of SARS-CoV-2 transcriptome and epitranscriptome using nanopore direct RNA sequencing and DNA nanoball sequencing.

  • The transcriptome is highly complex owing to numerous recombination events, both canonical and noncanonical.

  • In addition to the genomic and subgenomic RNAs common in all coronaviruses, SARS-CoV-2 produces transcripts encoding unknown ORFs.

  • We discover at least 41 potential RNA modification sites with an AAGAA motif.

Footnotes

  • ↵4 Lead Contact

  • https://osf.io/8f6n9/

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-NC-ND 4.0 International license.
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Posted March 15, 2020.
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The architecture of SARS-CoV-2 transcriptome
Dongwan Kim, Joo-Yeon Lee, Jeong-Sun Yang, Jun Won Kim, V. Narry Kim, Hyeshik Chang
bioRxiv 2020.03.12.988865; doi: https://doi.org/10.1101/2020.03.12.988865
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The architecture of SARS-CoV-2 transcriptome
Dongwan Kim, Joo-Yeon Lee, Jeong-Sun Yang, Jun Won Kim, V. Narry Kim, Hyeshik Chang
bioRxiv 2020.03.12.988865; doi: https://doi.org/10.1101/2020.03.12.988865

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