tetano
Editor, Senior Moderator
Nat Commun
. 2025 Sep 26;16(1):8460.
doi: 10.1038/s41467-025-63297-2. A conserved long-range RNA interaction in SARS-CoV-2 recruits ADAR1 to enhance virus proliferation
Siwy Ling Yang[SUP] #[/SUP][SUP] 1 [/SUP], Louis DeFalco[SUP] #[/SUP][SUP] 2 [/SUP], Sainan Wang[SUP] #[/SUP][SUP] 3 [/SUP], Yi Hao Wong[SUP] 4 [/SUP], Jian Han[SUP] 5 [/SUP], Chee Keng Mok[SUP] 6 [/SUP], Kiat Yee Tan[SUP] 5 [/SUP], Su Ying Lim[SUP] 5 [/SUP], Zhiya Zhao[SUP] 5 [/SUP], Yu Zhang[SUP] 5 [/SUP], Jovi Jian An Lim[SUP] 5 [/SUP], Joy S Xiang[SUP] 7 [/SUP], Radoslaw Sobota[SUP] 8 [/SUP], Lin-Fa Wang[SUP] 9 [/SUP], Justin Jang Hann Chu[SUP] 4 8 10 11 [/SUP], Andres Merits[SUP] 12 [/SUP], Roland G Huber[SUP] 13 [/SUP], Yue Wan[SUP] 14 15 16 [/SUP]
Affiliations
Long-range RNA-RNA pairing impacts the genome structure and function of SARS-CoV-2 variants. To understand the structure and function relationships of different SARS-CoV-2 variants that have emerged during the COVID-19 pandemic, we perform high-throughput structure probing and modelling of the genomic structures of the wildtype (WT), Alpha, Beta, Delta and Omicron variants of SARS-CoV-2. We observe that genomes of SARS-CoV-2 variants are generally structurally conserved, and that single-nucleotide variations and interactions with RNA binding proteins can impact RNA structures across the viruses. Importantly, using proximity ligation sequencing, we identify many conserved ultra-long-range RNA-RNA interactions, including one that spans more than 17 kb in both the WT virus and the Omicron variant. We show that mutations that disrupt this 17 kb long-range interaction reduce viral fitness at later stages of its infection cycle, while compensatory mutations partially restore virus fitness. Additionally, we show that this ultra-long-range RNA-RNA interaction structure binds directly to ADAR1 to alter the RNA editing levels on the viral genome. These studies deepen our understanding of RNA structures in the SARS-CoV-2 genome and their ability to interact with host factors to facilitate virus infectivity.
. 2025 Sep 26;16(1):8460.
doi: 10.1038/s41467-025-63297-2. A conserved long-range RNA interaction in SARS-CoV-2 recruits ADAR1 to enhance virus proliferation
Siwy Ling Yang[SUP] #[/SUP][SUP] 1 [/SUP], Louis DeFalco[SUP] #[/SUP][SUP] 2 [/SUP], Sainan Wang[SUP] #[/SUP][SUP] 3 [/SUP], Yi Hao Wong[SUP] 4 [/SUP], Jian Han[SUP] 5 [/SUP], Chee Keng Mok[SUP] 6 [/SUP], Kiat Yee Tan[SUP] 5 [/SUP], Su Ying Lim[SUP] 5 [/SUP], Zhiya Zhao[SUP] 5 [/SUP], Yu Zhang[SUP] 5 [/SUP], Jovi Jian An Lim[SUP] 5 [/SUP], Joy S Xiang[SUP] 7 [/SUP], Radoslaw Sobota[SUP] 8 [/SUP], Lin-Fa Wang[SUP] 9 [/SUP], Justin Jang Hann Chu[SUP] 4 8 10 11 [/SUP], Andres Merits[SUP] 12 [/SUP], Roland G Huber[SUP] 13 [/SUP], Yue Wan[SUP] 14 15 16 [/SUP]
Affiliations
- PMID: 41006205
- PMCID: PMC12475128
- DOI: 10.1038/s41467-025-63297-2
Long-range RNA-RNA pairing impacts the genome structure and function of SARS-CoV-2 variants. To understand the structure and function relationships of different SARS-CoV-2 variants that have emerged during the COVID-19 pandemic, we perform high-throughput structure probing and modelling of the genomic structures of the wildtype (WT), Alpha, Beta, Delta and Omicron variants of SARS-CoV-2. We observe that genomes of SARS-CoV-2 variants are generally structurally conserved, and that single-nucleotide variations and interactions with RNA binding proteins can impact RNA structures across the viruses. Importantly, using proximity ligation sequencing, we identify many conserved ultra-long-range RNA-RNA interactions, including one that spans more than 17 kb in both the WT virus and the Omicron variant. We show that mutations that disrupt this 17 kb long-range interaction reduce viral fitness at later stages of its infection cycle, while compensatory mutations partially restore virus fitness. Additionally, we show that this ultra-long-range RNA-RNA interaction structure binds directly to ADAR1 to alter the RNA editing levels on the viral genome. These studies deepen our understanding of RNA structures in the SARS-CoV-2 genome and their ability to interact with host factors to facilitate virus infectivity.