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Details on Person When bound to viral double-stranded RNA (dsRNA), 2′-5′-oligo...
| Class:Id | Summation:9985837 |
|---|---|
| _displayName | When bound to viral double-stranded RNA (dsRNA), 2′-5′-oligo... |
| _timestamp | 2026-03-26 20:44:25 |
| created | [InstanceEdit:9985788] Shamovsky, Veronica, 2026-03-26 |
| literatureReference | [LiteratureReference:9985995] Endomembrane targeting of human OAS1 p46 augments antiviral activity [LiteratureReference:9985920] A prenylated dsRNA sensor protects against severe COVID-19 [LiteratureReference:9716358] Rapid RNase L-driven arrest of protein synthesis in the dsRNA response without degradation of translation machinery [LiteratureReference:8983650] Structural basis for cytosolic double-stranded RNA surveillance by human oligoadenylate synthetase 1 [LiteratureReference:9985938] Enzyme assays for synthesis and degradation of 2-5As and other 2'-5' oligonucleotides [LiteratureReference:9012236] The Activation Mechanism of 2'-5'-Oligoadenylate Synthetase Gives New Insights Into OAS/cGAS Triggers of Innate Immunity [LiteratureReference:9614527] Viral phosphodiesterases that antagonize double-stranded RNA signaling to RNase L by degrading 2-5A [LiteratureReference:9012230] OAS proteins and cGAS: unifying concepts in sensing and responding to cytosolic nucleic acids [LiteratureReference:9012235] Viral encounters with 2',5'-oligoadenylate synthetase and RNase L during the interferon antiviral response |
| text | When bound to viral double-stranded RNA (dsRNA), 2′-5′-oligoadenylate synthetase 1 (OAS1) catalyzes the polymerization of ATP into 5′-triphosphorylated 2′-5′-linked oligoadenylates (2–5A). During this reaction, OAS1 transfers an AMP moiety from a donor ATP to the 2′-hydroxyl group of an acceptor substrate, which is either ATP or a preexisting 2–5A chain, forming dimeric (ppp5′A(2′-5′)A) or extended oligomers (ppp5'A((2'-5')A)n), with pyrophosphate (PPi) released at each elongation step (Lohofener J et al., 2015; Poulsen JB et al., 2015). Structural studies show that dsRNA engagement induces an allosteric rearrangement that stabilizes the ATP-binding cleft by repositioning catalytic residues D75, D77, and D148 to coordinate two Mg²⁺ ions and facilitate ATP binding (Donovan J et al., 2013). This conformational change effectively couples dsRNA recognition to OAS1 enzymatic activation. The resulting 2–5A molecules act as second messengers that bind and activate latent RNase L, promoting its dimerization and triggering degradation of viral and cellular single-stranded RNA, thereby inducing translation arrest and inhibition of viral replication (Donovan J et al., 2017; reviewed by Silverman RH, 2007; Hornung V et al., 2014). During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, viral genome replication occurs in endoplasmic reticulum (ER)–derived double-membrane vesicles (DMVs) that sequester dsRNA replication intermediates away from most cytosolic RNA sensors, including OAS1. However, the prenylated OAS1 p46 isoform, generated through allele-specific alternative splicing and CAAX-dependent geranylgeranylation, localizes to Golgi or ER membranes and relocalizes to SARS-CoV-2 replication organelles. This membrane association allows OAS1 p46 to access dsRNA protected within DMVs, enabling efficient activation of the OAS1–RNase L pathway against SARS-CoV-2 (Soveg FW et al., 2021; Wickenhagen A et al., 2021). |
| (summation) | [Reaction:9985802] SARS-CoV-2 dsRNA-bound GGC-OAS1 produces 2'-5' oligoadenylates [Homo sapiens] |
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