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

Authors

Zi Wen, Lei Chen, Dehua Luo, Ju Sun, Liangrong Guo, Yingxiang Deng, Zhiyuan Huang, Yuxiang Wang, Ke Pan, Fan Wang, Shaobo Xiao, Li Li, Dengguo Wei

Published in

Molecular systems biology. Jul 30, 2026. Epub Jul 30, 2026.

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.

PMID:
42533184
Bibliographic data and abstract were imported from PubMed on 31 Jul 2026.

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