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Peer-reviewedCC BY 4.0Molecular Systems Biology

Cross-genus analysis reveals architecturally programmed sgRNA synthesis patterns in coronaviruses

  • Zi Wen1,2,3,4
  • Lei Chen1,2,5
  • Dehua Luo1,2,5
  • Ju Sun1,2,5
  • Liangrong Guo1,2,5
  • Yingxiang Deng1,2,5
  • Zhiyuan Huang2,3
  • Yuxiang Wang1,2,5
  • Ke Pan1,2,5
  • Fan Wang6
  • Shaobo Xiao1
  • Li Li2,3
1 more authors
  • Dengguo Wei1,2,5,7,8,9
9 affiliations
  1. 1National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070 China
  2. 2Hubei Hongshan Laboratory, Interdisciplinary Sciences Institute, Huazhong Agricultural University, Wuhan, Hubei 430070 China
  3. 3College of Informatics, Huazhong Agricultural University, Wuhan, Hubei 430070 China
  4. 4Yazhou Bay National Laboratory, Sanya, Hainan 572024 China
  5. 5National Reference Laboratory of Veterinary Drug Residues (HZAU) and National Safety Laboratory of Veterinary Drug (HZAU), MOA Key Laboratory for Detection of Veterinary Drug Residues, MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, Hubei 430070 China
  6. 6National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, Central China Normal University, Wuhan, Hubei 430079 China
  7. 7Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan, Hubei 430070 China
  8. 8Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Shenzhen, 518000 China
  9. 9Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518000 China
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Abstract

Coronaviruses employ discontinuous transcription to produce canonical subgenomic RNAs (sgRNAs) essential for gene expression. Although TRS-dependent template switching mechanism has been proposed, its structural basis remains poorly defined, and the functional significance of abundant non-canonical sgRNAs persists as a critical gap since the discovery of discontinuous RNA synthesis. Here, we help bridge this gap through the first cross-genus integrated analysis of coronavirus transcriptomes and RNA interactomes. We show that canonical sgRNA formation is associated with same-direction RNA-RNA interactions. In contrast, non-canonical sgRNAs form through distinct architectural mechanisms: short-range junctions mediated by stem-loop structures overlapping genomic deletion hotspots, and conserved long-range ORF1a-N interactions generating sgRNAs encoding immune-modulatory ORFs — a function not previously attributed to non-canonical transcription. These findings suggest architecturally programmed discontinuous RNA synthesis and highlight a potential link between non-canonical sgRNAs, genomic plasticity, and immune modulation, which may have implications for coronavirus adaptation.

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Cite

BibTeXRIS
BibTeX
@article{wen2026crossgenus,
  title = {{Cross-genus analysis reveals architecturally programmed sgRNA synthesis patterns in coronaviruses}},
  author = {Zi Wen and Lei Chen and Dehua Luo and Ju Sun and Liangrong Guo and Yingxiang Deng and Zhiyuan Huang and Yuxiang Wang and Ke Pan and Fan Wang and Shaobo Xiao and Li Li and Dengguo Wei},
  journal = {Molecular Systems Biology},
  year = {2026},
  month = jul,
  doi = {10.1038/s44320-026-00239-0},
  url = {https://doi.org/10.1038/s44320-026-00239-0},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Cross-genus analysis reveals architecturally programmed sgRNA synthesis patterns in coronaviruses
AU  - Zi Wen
AU  - Lei Chen
AU  - Dehua Luo
AU  - Ju Sun
AU  - Liangrong Guo
AU  - Yingxiang Deng
AU  - Zhiyuan Huang
AU  - Yuxiang Wang
AU  - Ke Pan
AU  - Fan Wang
AU  - Shaobo Xiao
AU  - Li Li
AU  - Dengguo Wei
PY  - 2026
DA  - 2026/07/30
JO  - Molecular Systems Biology
DO  - 10.1038/s44320-026-00239-0
UR  - https://doi.org/10.1038/s44320-026-00239-0
AB  - Coronaviruses employ discontinuous transcription to produce canonical subgenomic RNAs (sgRNAs) essential for gene expression. Although TRS-dependent template switching mechanism has been proposed, its structural basis remains poorly defined, and the functional significance of abundant non-canonical sgRNAs persists as a critical gap since the discovery of discontinuous RNA synthesis. Here, we help bridge this gap through the first cross-genus integrated analysis of coronavirus transcriptomes and RNA interactomes. We show that canonical sgRNA formation is associated with same-direction RNA-RNA interactions. In contrast, non-canonical sgRNAs form through distinct architectural mechanisms: short-range junctions mediated by stem-loop structures overlapping genomic deletion hotspots, and conserved long-range ORF1a-N interactions generating sgRNAs encoding immune-modulatory ORFs — a function not previously attributed to non-canonical transcription. These findings suggest architecturally programmed discontinuous RNA synthesis and highlight a potential link between non-canonical sgRNAs, genomic plasticity, and immune modulation, which may have implications for coronavirus adaptation.
SN  - 1744-4292
ER  -