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.

      Article CAS PubMed PubMed Central Google Scholar

    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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    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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