Backbone resonance assignment of the third domain of the human staphylococcal nuclease domain-containing protein 1 (SND1).

Staphylococcal nuclease and Tudor domain‑containing protein 1 (SND1) is a multifunctional RNA‑binding protein implicated in transcriptional regulation, post‑transcriptional RNA control, oncogenesis, and viral infection. Initially identified as a transcriptional coactivator, SND1 was later established as a component of the RNA‑induced silencing complex, where it contributes to RNA turnover and microRNA regulation. SND1's diverse activities stem from its modular architecture, comprising four staphylococcal nuclease‑like domains, capable of direct RNA binding, and an extended Tudor domain that together form an integrated RNA‑binding and catalytic platform. This versatility also underlies its role in viral infection: SND1 acts as an m⁶A reader and is exploited by RNA viruses, such as SARS‑CoV‑2. Recent work showed that SND1 depletion, particularly loss of its third structured domain (SN3), reduces recruitment of the viral protein Nsp9 to the 3' untranslated region of the SARS‑CoV‑2 genome, impairing viral RNA synthesis through a direct SN3-Nsp9 interaction. Here, we report expression, purification, and near‑complete backbone NMR assignments of the SN3 domain of SND1. Secondary structure elements calculated by TALOS-N based on these assignments are in good agreement with the existing crystal structure of SN3. Our data provide an excellent foundation for future structural studies of SND1-RNA complexes and their roles in viral RNA priming in SARS-CoV-2.