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The Architecture of SARS-CoV-2 Transcriptome.

Dongwan Kim1, Joo-Yeon Lee2, Jeong-Sun Yang2

  • 1Center for RNA Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea; School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea.

Cell
|April 25, 2020
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Summary

This study maps the SARS-CoV-2 transcriptome and epitranscriptome, revealing complex RNA structures and over 40 modification sites. These findings offer new insights into the virus

Keywords:
COVID-19RNA modificationSARS-CoV-2coronavirusdirect RNA sequencingdiscontinuous transcriptionepitranscriptomenanoporepoly(A) tailtranscriptome

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Area of Science:

  • Virology
  • Molecular Biology
  • Genomics

Background:

  • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes the COVID-19 pandemic.
  • The SARS-CoV-2 genome is known, but its transcriptomic architecture remains largely uncharacterized.

Purpose of the Study:

  • To create a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome.
  • To identify novel viral transcripts and RNA modifications.

Main Methods:

  • Utilized DNA nanoball sequencing to analyze transcriptome complexity.
  • Employed nanopore direct RNA sequencing to identify RNA modifications.

Main Results:

  • Discovered a highly complex SARS-CoV-2 transcriptome with numerous discontinuous transcription events.
  • Identified canonical genomic RNA, 9 subgenomic RNAs, and novel transcripts with unknown ORFs (fusion, deletion, frameshift).
  • Found at least 41 RNA modification sites on viral transcripts, with AAGAA as the most frequent motif. Modified RNAs exhibited shorter poly(A) tails.

Conclusions:

  • The SARS-CoV-2 transcriptome is more complex than previously understood.
  • Discovery of novel transcripts and RNA modifications provides new avenues for studying viral life cycle and pathogenicity.
  • RNA modifications may influence viral RNA stability and function.