Patterns of Isoform Variation for N Gene Subgenomic mRNAs in Betacoronavirus Transcriptomes
The nucleocapsid (N) protein is the most expressed protein in later stages of SARS-CoV-2 infection with several important functions. It is translated from a subgenomic mRNA (sgmRNA) formed by template switching during transcription. A recently described translation initiation site (TIS) with a CTG c...
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2024-12-01
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| author | James J. Kelley Andrey Grigoriev |
| author_facet | James J. Kelley Andrey Grigoriev |
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| description | The nucleocapsid (N) protein is the most expressed protein in later stages of SARS-CoV-2 infection with several important functions. It is translated from a subgenomic mRNA (sgmRNA) formed by template switching during transcription. A recently described translation initiation site (TIS) with a CTG codon in the leader sequence (TIS-L) is out of frame with most structural and accessory genes including the N gene and may act as a translation suppressor. We analyzed multiple sequenced samples infected by SARS-CoV-2 and found that any single variant of this virus produces multiple isoforms of the N sgmRNA. The main isoform starting at TIS-L is out of frame, but two secondary dominant isoforms (present in nearly all samples) were found to restore the reading frame and likely involved in the regulation of N protein production. Analysis of sequenced samples infected by other coronaviruses revealed that such isoforms are also produced in their transcriptomes. In SARS-CoV, they restore the reading frame for a putative TIS (also a CTG codon) in the same relative position as in SARS-CoV-2. Positions of junction breakpoints relative to stem loop 3 in the 5′-UTR suggest similar mechanisms in SARS-CoV, SARS-CoV-2, and OC43, but not in MERS-CoV. These observations may be pertinent for antisense-based antiviral strategies. |
| format | Article |
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| institution | Kabale University |
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| spelling | doaj-art-c3efe697ee5842c6bdf01927af3d5ad42025-01-24T13:52:20ZengMDPI AGViruses1999-49152024-12-011713610.3390/v17010036Patterns of Isoform Variation for N Gene Subgenomic mRNAs in Betacoronavirus TranscriptomesJames J. Kelley0Andrey Grigoriev1Department of Biology, Center for Computational and Integrative Biology, Rutgers University, Camden, NJ 08102, USADepartment of Biology, Center for Computational and Integrative Biology, Rutgers University, Camden, NJ 08102, USAThe nucleocapsid (N) protein is the most expressed protein in later stages of SARS-CoV-2 infection with several important functions. It is translated from a subgenomic mRNA (sgmRNA) formed by template switching during transcription. A recently described translation initiation site (TIS) with a CTG codon in the leader sequence (TIS-L) is out of frame with most structural and accessory genes including the N gene and may act as a translation suppressor. We analyzed multiple sequenced samples infected by SARS-CoV-2 and found that any single variant of this virus produces multiple isoforms of the N sgmRNA. The main isoform starting at TIS-L is out of frame, but two secondary dominant isoforms (present in nearly all samples) were found to restore the reading frame and likely involved in the regulation of N protein production. Analysis of sequenced samples infected by other coronaviruses revealed that such isoforms are also produced in their transcriptomes. In SARS-CoV, they restore the reading frame for a putative TIS (also a CTG codon) in the same relative position as in SARS-CoV-2. Positions of junction breakpoints relative to stem loop 3 in the 5′-UTR suggest similar mechanisms in SARS-CoV, SARS-CoV-2, and OC43, but not in MERS-CoV. These observations may be pertinent for antisense-based antiviral strategies.https://www.mdpi.com/1999-4915/17/1/36coronavirusesSARS-CoV-2transcriptomeN genesubgenomic mRNA |
| spellingShingle | James J. Kelley Andrey Grigoriev Patterns of Isoform Variation for N Gene Subgenomic mRNAs in Betacoronavirus Transcriptomes Viruses coronaviruses SARS-CoV-2 transcriptome N gene subgenomic mRNA |
| title | Patterns of Isoform Variation for N Gene Subgenomic mRNAs in Betacoronavirus Transcriptomes |
| title_full | Patterns of Isoform Variation for N Gene Subgenomic mRNAs in Betacoronavirus Transcriptomes |
| title_fullStr | Patterns of Isoform Variation for N Gene Subgenomic mRNAs in Betacoronavirus Transcriptomes |
| title_full_unstemmed | Patterns of Isoform Variation for N Gene Subgenomic mRNAs in Betacoronavirus Transcriptomes |
| title_short | Patterns of Isoform Variation for N Gene Subgenomic mRNAs in Betacoronavirus Transcriptomes |
| title_sort | patterns of isoform variation for n gene subgenomic mrnas in betacoronavirus transcriptomes |
| topic | coronaviruses SARS-CoV-2 transcriptome N gene subgenomic mRNA |
| url | https://www.mdpi.com/1999-4915/17/1/36 |
| work_keys_str_mv | AT jamesjkelley patternsofisoformvariationforngenesubgenomicmrnasinbetacoronavirustranscriptomes AT andreygrigoriev patternsofisoformvariationforngenesubgenomicmrnasinbetacoronavirustranscriptomes |