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bioRxiv · 10.1101/2025.03.13.642953

RNA Architecture Underlies Discontinuous Transcription and Evolution of Coronavirus

Wen, Z.·Chen, L.·Luo, D.·Sun, J.·Guo, L.·Deng, Y.·Huang, Z.·Wang, Y.·Pan, K.·Wang, F.·Xiao, S.·Li, L.·Wei, D.
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Abstract

Coronaviruses employ discontinuous transcription to produce canonical subgenomic RNAs (sgRNAs) essential for gene expression, as well as non-canonical sgRNAs with unclear function. Nevertheless, the mechanisms regulating the balance between canonical and non-canonical sgRNAs throughout the viral replication cycle remain unknown. We conducted an integrated analysis on 234 transcriptome and 12 RNA-RNA interactome samples across various coronavirus genera. RNA-RNA interactions were identified between TRS-B and TRS-L flanking regions in the same genomic direction, correlating with the formation of canonical junctions. Non-canonical junctions frequently span short or long genomic distance, with short-range junctions generally mediated by reverse complementary stem-loops and coinciding with genomic deletion regions. Conserved long-range non-canonical sgRNAs were identified across different coronaviruses, and these sgRNAs harbor ORF10 or an evolving gene to suppress antiviral innate immune responses. This work establishes a structural framework that enables an understanding of the regulatory mechanism behind discontinuous transcription and the evolutionary pathway of coronaviruses. TeaserDeciphering coronavirus transcription and evolution: an integration analysis of transcriptome and RNA-RNA interactome. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=165 HEIGHT=200 SRC="FIGDIR/small/642953v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1c58502org.highwire.dtl.DTLVardef@9f87d7org.highwire.dtl.DTLVardef@18f3492org.highwire.dtl.DTLVardef@c49362_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Wen, Z., Chen, L., Luo, D., Sun, J., Guo, L., Deng, Y., Huang, Z., Wang, Y., Pan, K., Wang, F., Xiao, S., Li, L., Wei, D.. 2025-03-13. RNA Architecture Underlies Discontinuous Transcription and Evolution of Coronavirus. https://doi.org/10.1101/2025.03.13.642953

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