DNA G-Quadruplex in NRP1 Promoter Facilitates SARS-CoV-2 Infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to raise concerns worldwide. Numerous host factors involved in SARS-CoV-2 infection have been identified, but the regulatory mechanisms of these host factor remain unclear. Here, we report the role of G-quadruplexes (G4...

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Veröffentlicht in:International journal of molecular sciences 2024-04, Vol.25 (8), p.4422
Hauptverfasser: Gong, Pihai, Zhang, Rongxin, Xiao, Ke, Shu, Huiling, Li, Xinxiu, Fan, Hong, Sun, Xiao
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container_issue 8
container_start_page 4422
container_title International journal of molecular sciences
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creator Gong, Pihai
Zhang, Rongxin
Xiao, Ke
Shu, Huiling
Li, Xinxiu
Fan, Hong
Sun, Xiao
description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to raise concerns worldwide. Numerous host factors involved in SARS-CoV-2 infection have been identified, but the regulatory mechanisms of these host factor remain unclear. Here, we report the role of G-quadruplexes (G4s) located in the host factor promoter region in SARS-CoV-2 infection. Using bioinformatics, biochemical, and biological assays, we provide evidence for the presence of G4 structures in the promoter regions of SARS-CoV-2 host factors NRP1. Specifically, we focus on two representative G4s in the promoter and highlight its importance in SARS-CoV-2 pathogenesis. The presence of the G4 structure greatly increases NRP1 expression, facilitating SARS-CoV-2 entry into cells. Utilizing published single-cell RNA sequencing data obtained from simulated SARS-CoV-2 infection in human bronchial epithelial cells (HBECs), we found that ciliated cells with high levels of are prominently targeted by the virus during infection. Furthermore, our study identifies E2F1 act as a transcription factor that binds to G4s. These findings uncover a previously unknown mechanism underlying SARS-CoV-2 infection and suggest that targeting G4 structures could be a potential strategy for COVID-19 prevention and treatment.
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Numerous host factors involved in SARS-CoV-2 infection have been identified, but the regulatory mechanisms of these host factor remain unclear. Here, we report the role of G-quadruplexes (G4s) located in the host factor promoter region in SARS-CoV-2 infection. Using bioinformatics, biochemical, and biological assays, we provide evidence for the presence of G4 structures in the promoter regions of SARS-CoV-2 host factors NRP1. Specifically, we focus on two representative G4s in the promoter and highlight its importance in SARS-CoV-2 pathogenesis. The presence of the G4 structure greatly increases NRP1 expression, facilitating SARS-CoV-2 entry into cells. Utilizing published single-cell RNA sequencing data obtained from simulated SARS-CoV-2 infection in human bronchial epithelial cells (HBECs), we found that ciliated cells with high levels of are prominently targeted by the virus during infection. Furthermore, our study identifies E2F1 act as a transcription factor that binds to G4s. 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source MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; PubMed Central; EZB Electronic Journals Library
subjects Coronaviruses
COVID-19
COVID-19 - genetics
COVID-19 - virology
DNA
E2F1 Transcription Factor - genetics
E2F1 Transcription Factor - metabolism
Epithelial Cells - metabolism
Epithelial Cells - virology
Experiments
G-Quadruplexes
Health aspects
Humans
Infections
Medical research
Medicine, Experimental
Neuropilin-1 - genetics
Neuropilin-1 - metabolism
Pandemics
Promoter Regions, Genetic
Proteins
RNA
RNA sequencing
SARS-CoV-2 - physiology
Scientific equipment and supplies industry
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Virus Internalization
Viruses
title DNA G-Quadruplex in NRP1 Promoter Facilitates SARS-CoV-2 Infection
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