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Crystal structure of an adenovirus virus-associated RNA

Author

Listed:
  • Iris V. Hood

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Jackson M. Gordon

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Charles Bou-Nader

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Frances E. Henderson

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Soheila Bahmanjah

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Jinwei Zhang

    (National Institute of Diabetes and Digestive and Kidney Diseases)

Abstract

Adenovirus Virus-Associated (VA) RNAs are the first discovered viral noncoding RNAs. By mimicking double-stranded RNAs (dsRNAs), the exceptionally abundant, multifunctional VA RNAs sabotage host machineries that sense, transport, process, or edit dsRNAs. How VA-I suppresses PKR activation despite its strong dsRNA character, and inhibits the crucial antiviral kinase to promote viral translation, remains largely unknown. Here, we report a 2.7 Å crystal structure of VA-I RNA. The acutely bent VA-I features an unusually structured apical loop, a wobble-enriched, coaxially stacked apical and tetra-stems necessary and sufficient for PKR inhibition, and a central domain pseudoknot that resembles codon-anticodon interactions and prevents PKR activation by VA-I. These global and local structural features collectively define VA-I as an archetypal PKR inhibitor made of RNA. The study provides molecular insights into how viruses circumnavigate cellular rules of self vs non-self RNAs to not only escape, but further compromise host innate immunity.

Suggested Citation

  • Iris V. Hood & Jackson M. Gordon & Charles Bou-Nader & Frances E. Henderson & Soheila Bahmanjah & Jinwei Zhang, 2019. "Crystal structure of an adenovirus virus-associated RNA," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10752-6
    DOI: 10.1038/s41467-019-10752-6
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    Cited by:

    1. Krishna C. Suddala & Janghyun Yoo & Lixin Fan & Xiaobing Zuo & Yun-Xing Wang & Hoi Sung Chung & Jinwei Zhang, 2023. "Direct observation of tRNA-chaperoned folding of a dynamic mRNA ensemble," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Charles Bou-Nader & Ankur Bothra & David N. Garboczi & Stephen H. Leppla & Jinwei Zhang, 2022. "Structural basis of R-loop recognition by the S9.6 monoclonal antibody," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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