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

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 metatranscriptomi...

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Main Authors: Xinxin Peng, Yikai Luo, Hongyue Li, Xuejiao Guo, Hu Chen, Xuwo Ji, Han Liang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-03-01
Series:PLoS Genetics
Online Access:https://doi.org/10.1371/journal.pgen.1010130
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author Xinxin Peng
Yikai Luo
Hongyue Li
Xuejiao Guo
Hu Chen
Xuwo Ji
Han Liang
author_facet Xinxin Peng
Yikai Luo
Hongyue Li
Xuejiao Guo
Hu Chen
Xuwo Ji
Han Liang
author_sort Xinxin Peng
collection DOAJ
description 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.
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spelling doaj.art-c1cfe67035ef4058a9c6fc0769dad1532022-12-22T00:37:25ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042022-03-01183e101013010.1371/journal.pgen.1010130RNA editing increases the nucleotide diversity of SARS-CoV-2 in human host cells.Xinxin PengYikai LuoHongyue LiXuejiao GuoHu ChenXuwo JiHan LiangSARS-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.https://doi.org/10.1371/journal.pgen.1010130
spellingShingle Xinxin Peng
Yikai Luo
Hongyue Li
Xuejiao Guo
Hu Chen
Xuwo Ji
Han Liang
RNA editing increases the nucleotide diversity of SARS-CoV-2 in human host cells.
PLoS Genetics
title RNA editing increases the nucleotide diversity of SARS-CoV-2 in human host cells.
title_full RNA editing increases the nucleotide diversity of SARS-CoV-2 in human host cells.
title_fullStr RNA editing increases the nucleotide diversity of SARS-CoV-2 in human host cells.
title_full_unstemmed RNA editing increases the nucleotide diversity of SARS-CoV-2 in human host cells.
title_short RNA editing increases the nucleotide diversity of SARS-CoV-2 in human host cells.
title_sort rna editing increases the nucleotide diversity of sars cov 2 in human host cells
url https://doi.org/10.1371/journal.pgen.1010130
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