{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:41:51Z","timestamp":1760146911495,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Foundation","award":["MCB-2027611"],"award-info":[{"award-number":["MCB-2027611"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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\u2032-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.<\/jats:p>","DOI":"10.3390\/v17010036","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T13:26:25Z","timestamp":1735651585000},"page":"36","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Patterns of Isoform Variation for N Gene Subgenomic mRNAs in Betacoronavirus Transcriptomes"],"prefix":"10.3390","volume":"17","author":[{"given":"James J.","family":"Kelley","sequence":"first","affiliation":[{"name":"Department of Biology, Center for Computational and Integrative Biology, Rutgers University, Camden, NJ 08102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3227-532X","authenticated-orcid":false,"given":"Andrey","family":"Grigoriev","sequence":"additional","affiliation":[{"name":"Department of Biology, Center for Computational and Integrative Biology, Rutgers University, Camden, NJ 08102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.tig.2004.01.009","article-title":"Mutational patterns correlate with genome organization in SARS and other coronaviruses","volume":"20","author":"Grigoriev","year":"2004","journal-title":"Trends Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/j.cell.2020.04.011","article-title":"The architecture of SARS-CoV-2 transcriptome","volume":"181","author":"Kim","year":"2020","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"135201","DOI":"10.1016\/j.ijbiomac.2024.135201","article-title":"Unraveling the role of the nucleocapsid protein in SARS-CoV-2 pathogenesis: From viral life cycle to vaccine development","volume":"279","author":"Badawy","year":"2024","journal-title":"Int. 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