Cross-genus analysis reveals architecturally programmed sgRNA synthesis patterns in coronaviruses
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.
Authors
- Yuxiang Wang (ORCID: https://orcid.org/0009-0009-3914-4486)
- Dengguo Wei (ORCID: https://orcid.org/0000-0001-9923-789X)
- Dehua Luo
- Fan Wang (ORCID: https://orcid.org/0000-0003-2664-9214)
- Shaobo Xiao (ORCID: https://orcid.org/0000-0003-0023-9188)
- Zi Wen (ORCID: https://orcid.org/0000-0001-7600-4399)
- Ju Sun (ORCID: https://orcid.org/0009-0002-6157-1790)
- Li Li (ORCID: https://orcid.org/0000-0002-9594-8341)
- Zhiyuan Huang (ORCID: https://orcid.org/0000-0003-1284-2128)
- Ke Pan (ORCID: https://orcid.org/0000-0003-2667-9026)
- L Y Guo (ORCID: https://orcid.org/0000-0002-4219-9498)
- Yingxiang Deng
- Lei Chen
Institutions
- Huazhong Agricultural University (CN)
- Central China Normal University (CN)
- Agricultural Genomics Institute at Shenzhen (CN)
- Ministry of Education (ME)
- China Institute of Veterinary Drug Control (CN)
- Shenzhen University Health Science Center (CN)
- Sanya University (CN)
- Center of Hubei Cooperative Innovation for Emissions Trading System (CN)
Publication Details
- Journal
- Molecular Systems Biology
- Published
- 2026-07-30
- DOI
- https://doi.org/10.1038/s44320-026-00239-0
- Primary Topic
- RNA regulation and disease
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Ministry of Education of the People's Republic of China
- Huazhong Agricultural University
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities