A Negative Feedback Model to Explain Regulation of SARS-CoV-2 Replication and Transcription
BackgroundCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a preliminary understanding of the replication and transcription of SARS-CoV-2 has recently emerged, their regulation remains unknown.ResultsBy comprehensive analysis of...
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.641445/full |
| _version_ | 1818441691614412800 |
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| author | Xin Li Xin Li Zhi Cheng Fang Wang Jia Chang Qiang Zhao Hao Zhou Chang Liu Jishou Ruan Guangyou Duan Shan Gao |
| author_facet | Xin Li Xin Li Zhi Cheng Fang Wang Jia Chang Qiang Zhao Hao Zhou Chang Liu Jishou Ruan Guangyou Duan Shan Gao |
| author_sort | Xin Li |
| collection | DOAJ |
| description | BackgroundCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a preliminary understanding of the replication and transcription of SARS-CoV-2 has recently emerged, their regulation remains unknown.ResultsBy comprehensive analysis of genome sequence and protein structure data, we propose a negative feedback model to explain the regulation of CoV replication and transcription, providing a molecular basis of the “leader-to-body fusion” model. The key step leading to the proposal of our model was that the transcription regulatory sequence (TRS) motifs were identified as the cleavage sites of nsp15, a nidoviral RNA uridylate-specific endoribonuclease (NendoU). According to this model, nsp15 regulates the synthesis of subgenomic RNAs (sgRNAs), and genomic RNAs (gRNAs) by cleaving TRSs. The expression level of nsp15 controls the relative proportions of sgRNAs and gRNAs, which in turn change the expression level of nsp15 to reach equilibrium between the CoV replication and transcription.ConclusionThe replication and transcription of CoVs are regulated by a negative feedback mechanism that influences the persistence of CoVs in hosts. Our findings enrich fundamental knowledge in the field of gene expression and its regulation, and provide new clues for future studies. One important clue is that nsp15 may be an important and ideal target for the development of drugs (e.g., uridine derivatives) against CoVs. |
| first_indexed | 2024-12-14T18:32:17Z |
| format | Article |
| id | doaj.art-7272571158c945729950917f39a6a95a |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-14T18:32:17Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-7272571158c945729950917f39a6a95a2022-12-21T22:51:44ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-02-011210.3389/fgene.2021.641445641445A Negative Feedback Model to Explain Regulation of SARS-CoV-2 Replication and TranscriptionXin Li0Xin Li1Zhi Cheng2Fang Wang3Jia Chang4Qiang Zhao5Hao Zhou6Chang Liu7Jishou Ruan8Guangyou Duan9Shan Gao10College of Life Sciences, Nankai University, Tianjin, ChinaThe Second Hospital of Tianjin Medical University, Tianjin, ChinaState Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, ChinaThe Second Hospital of Tianjin Medical University, Tianjin, ChinaCollege of Life Sciences, Nankai University, Tianjin, ChinaCollege of Life Sciences, Nankai University, Tianjin, ChinaCollege of Life Sciences, Nankai University, Tianjin, ChinaCollege of Life Sciences, Nankai University, Tianjin, ChinaSchool of Mathematical Sciences, Nankai University, Tianjin, ChinaSchool of Life Sciences, Qilu Normal University, Jinan, ChinaCollege of Life Sciences, Nankai University, Tianjin, ChinaBackgroundCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a preliminary understanding of the replication and transcription of SARS-CoV-2 has recently emerged, their regulation remains unknown.ResultsBy comprehensive analysis of genome sequence and protein structure data, we propose a negative feedback model to explain the regulation of CoV replication and transcription, providing a molecular basis of the “leader-to-body fusion” model. The key step leading to the proposal of our model was that the transcription regulatory sequence (TRS) motifs were identified as the cleavage sites of nsp15, a nidoviral RNA uridylate-specific endoribonuclease (NendoU). According to this model, nsp15 regulates the synthesis of subgenomic RNAs (sgRNAs), and genomic RNAs (gRNAs) by cleaving TRSs. The expression level of nsp15 controls the relative proportions of sgRNAs and gRNAs, which in turn change the expression level of nsp15 to reach equilibrium between the CoV replication and transcription.ConclusionThe replication and transcription of CoVs are regulated by a negative feedback mechanism that influences the persistence of CoVs in hosts. Our findings enrich fundamental knowledge in the field of gene expression and its regulation, and provide new clues for future studies. One important clue is that nsp15 may be an important and ideal target for the development of drugs (e.g., uridine derivatives) against CoVs.https://www.frontiersin.org/articles/10.3389/fgene.2021.641445/fullcoronavirustranscriptionreplicationregulation modelnsp15 |
| spellingShingle | Xin Li Xin Li Zhi Cheng Fang Wang Jia Chang Qiang Zhao Hao Zhou Chang Liu Jishou Ruan Guangyou Duan Shan Gao A Negative Feedback Model to Explain Regulation of SARS-CoV-2 Replication and Transcription Frontiers in Genetics coronavirus transcription replication regulation model nsp15 |
| title | A Negative Feedback Model to Explain Regulation of SARS-CoV-2 Replication and Transcription |
| title_full | A Negative Feedback Model to Explain Regulation of SARS-CoV-2 Replication and Transcription |
| title_fullStr | A Negative Feedback Model to Explain Regulation of SARS-CoV-2 Replication and Transcription |
| title_full_unstemmed | A Negative Feedback Model to Explain Regulation of SARS-CoV-2 Replication and Transcription |
| title_short | A Negative Feedback Model to Explain Regulation of SARS-CoV-2 Replication and Transcription |
| title_sort | negative feedback model to explain regulation of sars cov 2 replication and transcription |
| topic | coronavirus transcription replication regulation model nsp15 |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.641445/full |
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