Summary information and primary citation

PDB-id
9cfn; DSSR-derived features in text and JSON formats
Class
RNA
Method
X-ray (2.9 Å)
Summary
Crystal structure of an exoribonuclease-resistant RNA from a tombusvirus-like associated RNA
Reference
Gezelle JG, Korn SM, McDonald JT, Gong Z, Erickson A, Huang CH, Yang F, Cronin M, Kuo YW, Wimberly BT, Steckelberg AL (2025): "A conserved viral RNA fold enables nuclease resistance across kingdoms of life." Nucleic Acids Res., 53. doi: 10.1093/nar/gkaf840.
Abstract
Viral exoribonuclease-resistant RNA (xrRNA) structures block cellular nucleases to produce subgenomic viral RNAs during infection. High sequence variability among xrRNAs from distantly related viruses raises questions about the shared molecular features that enable these RNAs to withstand the strong unwinding forces of exoribonucleases. Here, we present the first structure of a plant-virus xrRNA in its active conformation and uncover universal principles of xrRNA folding. Comparison with the structure of a human-pathogenic flavivirus xrRNA reveals that both share a core structural motif-a protective ring encircling the RNA's 5' end-despite lacking sequence similarity. Disrupting this core motif through targeted mutagenesis eliminates exoribonuclease-resistance and attenuates viral infection. We identify hundreds of related structures across multiple virus families, supporting the conservation of this mechanism. Our study demonstrates how distantly related RNA viruses have converged on a common structural strategy to inhibit cellular nucleases, with a universal ring topology as the defining feature of viral xrRNAs.

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