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Epitranscriptomic m6A profile of SARS-CoV-2-infected human lung epithelial cells

SARS-CoV-2感染的人肺上皮细胞的表观转录组m6A谱

基本信息

批准号：
10297640
负责人：
Li Wu
金额：
$ 19.31万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10297640
关键词：
2019-nCoV Address Affect Antiviral Agents Attenuated Bioinformatics COVID-19 COVID-19 pandemic COVID-19 pathogenesis COVID-19 treatment Cells Chemicals Clinical Collaborations Coronavirus Coronavirus Infections Cytokine Gene Data Development Epithelial Cells Foundations Future Gene Expression Gene Expression Regulation Genes HIV-1 Hour Human Immune Evasion Immunoprecipitation Infection Inflammatory Interferon Type I Interferons Italy Left Length Lung Maps Messenger RNA Modification Molecular Nucleotides Organism Pathogenicity Patients Pharmaceutical Preparations Play Post-Transcriptional Regulation RNA Regulation Role SARS-CoV-2 genome SARS-CoV-2 infection Site Technology Testing Vaccines Viral Genes Viral Genome Viral Pathogenesis Virus Virus Replication base cellular targeting cytokine cytokine release syndrome epitranscriptomics genomic RNA global health health economics mRNA Expression mutant new therapeutic target novel prevent severe COVID-19 therapeutically effective transcriptome sequencing vaccine candidate

项目摘要

Abstract The COVID-19 pandemic caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in global health and economic crises. To develop effective vaccines and antivirals to prevent and control SARS-CoV-2 or other coronavirus infections, it is critical to understand the regulatory mechanisms of SARS-CoV-2 genome replication in host cells. In this R21 project, we will use novel epitranscriptomic technologies to investigate SARS-CoV-2 replication in human lung epithelial cells. N6-methyladenosine (m6A) modifications of many viruses play a major role in epitranscriptomic regulation of viral replication, gene expression, and immune evasion. However, it is unclear whether and how m6A modifications of the SARS-CoV-2 genome and cellular genes affect viral replication and pathogenicity. Our preliminary studies showed that SARS-CoV-2 infection of human lung epithelial cells upregulated m6A levels in cellular RNA. Our bioinformatic analysis of 13,699 full-length SARS- CoV-2 genome sequences predicts multiple m6A modification sites that are highly conserved among SARS-CoV-2 isolates worldwide. Thus, we hypothesize that m6A modifications of the SARS-CoV-2 genome and cellular genes enhance viral replication in cells through epitranscriptomic regulation. We propose two specific aims to test this hypothesis. Aim 1. To investigate the m6A epitranscriptomic profile of SARS-CoV-2-infected lung epithelial cells; Aim 2. To map m6A sites on the SARS-CoV-2 genome and to identify critical sites for viral replication. Defining epitranscriptomic m6A profile of SARS-CoV-2-infected cells has significant implications in understanding the COVID-19 pathogenesis and identifying novel drug targets.

摘要