RNA editing increases the nucleotide diversity of SARS-CoV-2 in human host cells

PLoS Genet. 2022 Mar 30;18(3):e1010130. doi: 10.1371/journal.pgen.1010130. eCollection 2022 Mar.

Abstract

SARS-CoV-2 is a positive-sense, single-stranded RNA virus responsible for the COVID-19 pandemic. It remains unclear whether and to what extent the virus in human host cells undergoes RNA editing, a major RNA modification mechanism. Here we perform a robust bioinformatic analysis of metatranscriptomic data from multiple bronchoalveolar lavage fluid samples of COVID-19 patients, revealing an appreciable number of A-to-I RNA editing candidate sites in SARS-CoV-2. We confirm the enrichment of A-to-I RNA editing signals at these candidate sites through evaluating four characteristics specific to RNA editing: the inferred RNA editing sites exhibit (i) stronger ADAR1 binding affinity predicted by a deep-learning model built from ADAR1 CLIP-seq data, (ii) decreased editing levels in ADAR1-inhibited human lung cells, (iii) local clustering patterns, and (iv) higher RNA secondary structure propensity. Our results have critical implications in understanding the evolution of SARS-CoV-2 as well as in COVID-19 research, such as phylogenetic analysis and vaccine development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Deaminase / metabolism
  • COVID-19* / genetics
  • Humans
  • Nucleotides / metabolism
  • Pandemics
  • Phylogeny
  • RNA / metabolism
  • RNA Editing / genetics
  • SARS-CoV-2* / genetics

Substances

  • Nucleotides
  • RNA
  • Adenosine Deaminase

Grants and funding

We gratefully acknowledge the support from the Suzhou New District, Jiangsu Province, China (http://www.snd.gov.cn) (to X.P. and X.J.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.