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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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. |
doi_str_mv | 10.3390/ijms25084422 |
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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.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms25084422</identifier><identifier>PMID: 38674009</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>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</subject><ispartof>International journal of molecular sciences, 2024-04, Vol.25 (8), p.4422</ispartof><rights>COPYRIGHT 2024 MDPI AG</rights><rights>2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c381t-f6df912c4c5218ee8006420669e0656207903eb7b4e8c922b5f6ca9bd27ea1523</cites><orcidid>0000-0003-1048-7775 ; 0000-0002-2783-7850</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38674009$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gong, Pihai</creatorcontrib><creatorcontrib>Zhang, Rongxin</creatorcontrib><creatorcontrib>Xiao, Ke</creatorcontrib><creatorcontrib>Shu, Huiling</creatorcontrib><creatorcontrib>Li, Xinxiu</creatorcontrib><creatorcontrib>Fan, Hong</creatorcontrib><creatorcontrib>Sun, Xiao</creatorcontrib><title>DNA G-Quadruplex in NRP1 Promoter Facilitates SARS-CoV-2 Infection</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><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.</description><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>COVID-19 - genetics</subject><subject>COVID-19 - virology</subject><subject>DNA</subject><subject>E2F1 Transcription Factor - genetics</subject><subject>E2F1 Transcription Factor - metabolism</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial Cells - virology</subject><subject>Experiments</subject><subject>G-Quadruplexes</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Infections</subject><subject>Medical research</subject><subject>Medicine, Experimental</subject><subject>Neuropilin-1 - genetics</subject><subject>Neuropilin-1 - metabolism</subject><subject>Pandemics</subject><subject>Promoter Regions, Genetic</subject><subject>Proteins</subject><subject>RNA</subject><subject>RNA sequencing</subject><subject>SARS-CoV-2 - physiology</subject><subject>Scientific equipment and supplies industry</subject><subject>Severe acute respiratory syndrome</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Virus Internalization</subject><subject>Viruses</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptkc1r20AQxZeQEKdJbj0XQS49VO7sp7RH1_mowSSuk_YqVqtRWSNpnV0Jkv--MknzUcoc3jD83vDgEfKRwpRzDV_dpo1MQi4EY3vkiI6SAqhs_80-IR9i3AAwzqQ-JBOeq0wA6CPy7fx6llylPwZThWHb4EPiuuR6vaLJKvjW9xiSS2Nd43rTY0xuZ-vbdO5_pSxZdDXa3vnuhBzUpol4-qzH5Oflxd38e7q8uVrMZ8vU8pz2aa2qWlNmhZWM5oj5GEwwUEojKKkYZBo4llkpMLeasVLWyhpdVixDQyXjx-Tz099t8PcDxr5oXbTYNKZDP8SCg8i00DLLR_TsH3Tjh9CN6XaU0lRQyl6p36bBwnW174Oxu6fFLNNcSgCqR2r6H2qcCltnfYe1G-_vDF-eDDb4GAPWxTa41oTHgkKxq6x4W9mIf3rOOpQtVi_w3474HxIVi9U</recordid><startdate>20240401</startdate><enddate>20240401</enddate><creator>Gong, Pihai</creator><creator>Zhang, Rongxin</creator><creator>Xiao, Ke</creator><creator>Shu, Huiling</creator><creator>Li, Xinxiu</creator><creator>Fan, Hong</creator><creator>Sun, Xiao</creator><general>MDPI AG</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>COVID</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1048-7775</orcidid><orcidid>https://orcid.org/0000-0002-2783-7850</orcidid></search><sort><creationdate>20240401</creationdate><title>DNA G-Quadruplex in NRP1 Promoter Facilitates SARS-CoV-2 Infection</title><author>Gong, Pihai ; Zhang, Rongxin ; Xiao, Ke ; Shu, Huiling ; Li, Xinxiu ; Fan, Hong ; Sun, Xiao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-f6df912c4c5218ee8006420669e0656207903eb7b4e8c922b5f6ca9bd27ea1523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>COVID-19 - genetics</topic><topic>COVID-19 - virology</topic><topic>DNA</topic><topic>E2F1 Transcription Factor - genetics</topic><topic>E2F1 Transcription Factor - metabolism</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelial Cells - virology</topic><topic>Experiments</topic><topic>G-Quadruplexes</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Infections</topic><topic>Medical research</topic><topic>Medicine, Experimental</topic><topic>Neuropilin-1 - genetics</topic><topic>Neuropilin-1 - metabolism</topic><topic>Pandemics</topic><topic>Promoter Regions, Genetic</topic><topic>Proteins</topic><topic>RNA</topic><topic>RNA sequencing</topic><topic>SARS-CoV-2 - physiology</topic><topic>Scientific equipment and supplies industry</topic><topic>Severe acute respiratory syndrome</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Virus Internalization</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gong, Pihai</creatorcontrib><creatorcontrib>Zhang, Rongxin</creatorcontrib><creatorcontrib>Xiao, Ke</creatorcontrib><creatorcontrib>Shu, Huiling</creatorcontrib><creatorcontrib>Li, Xinxiu</creatorcontrib><creatorcontrib>Fan, Hong</creatorcontrib><creatorcontrib>Sun, Xiao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest research library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest - Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gong, Pihai</au><au>Zhang, Rongxin</au><au>Xiao, Ke</au><au>Shu, Huiling</au><au>Li, Xinxiu</au><au>Fan, Hong</au><au>Sun, Xiao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA G-Quadruplex in NRP1 Promoter Facilitates SARS-CoV-2 Infection</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2024-04-01</date><risdate>2024</risdate><volume>25</volume><issue>8</issue><spage>4422</spage><pages>4422-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>38674009</pmid><doi>10.3390/ijms25084422</doi><orcidid>https://orcid.org/0000-0003-1048-7775</orcidid><orcidid>https://orcid.org/0000-0002-2783-7850</orcidid><oa>free_for_read</oa></addata></record> |
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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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