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TnpB structure reveals minimal functional core of Cas12 nuclease family

Author

Listed:
  • Giedrius Sasnauskas

    (Vilnius University)

  • Giedre Tamulaitiene

    (Vilnius University)

  • Gytis Druteika

    (Vilnius University)

  • Arturo Carabias

    (University of Copenhagen)

  • Arunas Silanskas

    (Vilnius University)

  • Darius Kazlauskas

    (Vilnius University)

  • Česlovas Venclovas

    (Vilnius University)

  • Guillermo Montoya

    (University of Copenhagen)

  • Tautvydas Karvelis

    (Vilnius University)

  • Virginijus Siksnys

    (Vilnius University)

Abstract

The widespread TnpB proteins of IS200/IS605 transposon family have recently emerged as the smallest RNA-guided nucleases capable of targeted genome editing in eukaryotic cells1,2. Bioinformatic analysis identified TnpB proteins as the likely predecessors of Cas12 nucleases3–5, which along with Cas9 are widely used for targeted genome manipulation. Whereas Cas12 family nucleases are well characterized both biochemically and structurally6, the molecular mechanism of TnpB remains unknown. Here we present the cryogenic-electron microscopy structures of the Deinococcus radiodurans TnpB–reRNA (right-end transposon element-derived RNA) complex in DNA-bound and -free forms. The structures reveal the basic architecture of TnpB nuclease and the molecular mechanism for DNA target recognition and cleavage that is supported by biochemical experiments. Collectively, these results demonstrate that TnpB represents the minimal structural and functional core of the Cas12 protein family and provide a framework for developing TnpB-based genome editing tools.

Suggested Citation

  • Giedrius Sasnauskas & Giedre Tamulaitiene & Gytis Druteika & Arturo Carabias & Arunas Silanskas & Darius Kazlauskas & Česlovas Venclovas & Guillermo Montoya & Tautvydas Karvelis & Virginijus Siksnys, 2023. "TnpB structure reveals minimal functional core of Cas12 nuclease family," Nature, Nature, vol. 616(7956), pages 384-389, April.
    • Handle: RePEc:nat:nature:v:616:y:2023:i:7956:d:10.1038_s41586-023-05826-x
    DOI: 10.1038/s41586-023-05826-x
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    Cited by:

    1. Xu Feng & Ruyi Xu & Jianglan Liao & Jingyu Zhao & Baochang Zhang & Xiaoxiao Xu & Pengpeng Zhao & Xiaoning Wang & Jianyun Yao & Pengxia Wang & Xiaoxue Wang & Wenyuan Han & Qunxin She, 2024. "Flexible TAM requirement of TnpB enables efficient single-nucleotide editing with expanded targeting scope," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Zhifang Li & Ruochen Guo & Xiaozhi Sun & Guoling Li & Zhuang Shao & Xiaona Huo & Rongrong Yang & Xinyu Liu & Xi Cao & Hainan Zhang & Weihong Zhang & Xiaoyin Zhang & Shuangyu Ma & Meiling Zhang & Yuanh, 2024. "Engineering a transposon-associated TnpB-ωRNA system for efficient gene editing and phenotypic correction of a tyrosinaemia mouse model," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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