High-throughput screening of TnpB proteins identifies hypercompact genome editors

    Nature Biotechnology (2023)Cite this article

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    TnpB proteins are hypercompact RNA-guided DNA endonucleases. By systematically mining and characterizing TnpB proteins from the IS605 family, we identified potent genome editors and established a framework for high-throughput annotation and screening of TnpB systems in prokaryotic genomes.

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    Fig. 1: Phylogenetic sampling of TnpBs and the de novo discovery platform.

    References

    1. Altae-Tran, H. et al. The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases. Science 37457–65 (2021). This paper characterizes IscB and TnpB, demonstrates IscB’s activity in human cells and reconstructs the evolutionary relationships among IscB, TnpB and Cas proteins.

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    2. Karvelis, T. et al. Transposon-associated TnpB is a programmable RNA-guided DNA endonuclease. Nature 599692–696 (2021). This paper reports TnpB’s cleavage activity in human cells and proposes the expansion mechanism of IS200/IS605.

      Article CAS PubMed PubMed Central Google Scholar

    3. Nakagawa, R. et al. Cryo-EM structure of the transposon-associated TnpB enzyme. Nature 616390–397 (2023). This paper reports the cryo-electron microscopy structure of the ISDra2 TnpB–reRNA–dsDNA complex.

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    4. Sasnauskas, G. et al. TnpB structure reveals minimal functional core of Cas12 nuclease family. Nature 616384–389 (2023). This paper reports the structure of the ISDra2 TnpB–reRNA–dsDNA complex in relation to the Cas12 family.

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    5. Dobzhansky, T. Nothing in biology makes sense except in the light of evolution. Am. Biol. Teach. 35125–129 (1973). In this essay, Dobzhansky introduces the title precept.

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    Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

    This is a summary of: Xiang, G. et al. Evolutionary mining and functional characterization of TnpB nucleases identify efficient miniature genome editors. Nat. Biotechnol. https://doi.org/10.1038/s41587-023-01857-x (2023).

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    High-throughput screening of TnpB proteins identifies hypercompact genome editors. Nat Biotechnol (2023). https://doi.org/10.1038/s41587-023-01858-w

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    • DOI: https://doi.org/10.1038/s41587-023-01858-w

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