TnpB structure reveals minimal functional core of Cas12 nuclease family

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

TnpB structure reveals minimal functional core of Cas12 nuclease family. / Sasnauskas, Giedrius; Tamulaitiene, Giedre; Druteika, Gytis; Carabias, Arturo; Silanskas, Arunas; Kazlauskas, Darius; Venclovas, Česlovas; Montoya, Guillermo; Karvelis, Tautvydas; Siksnys, Virginijus.

In: Nature, Vol. 616, No. 7956, 2023, p. 384-389.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Sasnauskas, G, Tamulaitiene, G, Druteika, G, Carabias, A, Silanskas, A, Kazlauskas, D, Venclovas, Č, Montoya, G, Karvelis, T & Siksnys, V 2023, 'TnpB structure reveals minimal functional core of Cas12 nuclease family', Nature, vol. 616, no. 7956, pp. 384-389. https://doi.org/10.1038/s41586-023-05826-x

APA

Sasnauskas, G., Tamulaitiene, G., Druteika, G., Carabias, A., Silanskas, A., Kazlauskas, D., Venclovas, Č., Montoya, G., Karvelis, T., & Siksnys, V. (2023). TnpB structure reveals minimal functional core of Cas12 nuclease family. Nature, 616(7956), 384-389. https://doi.org/10.1038/s41586-023-05826-x

Vancouver

Sasnauskas G, Tamulaitiene G, Druteika G, Carabias A, Silanskas A, Kazlauskas D et al. TnpB structure reveals minimal functional core of Cas12 nuclease family. Nature. 2023;616(7956):384-389. https://doi.org/10.1038/s41586-023-05826-x

Author

Sasnauskas, Giedrius ; Tamulaitiene, Giedre ; Druteika, Gytis ; Carabias, Arturo ; Silanskas, Arunas ; Kazlauskas, Darius ; Venclovas, Česlovas ; Montoya, Guillermo ; Karvelis, Tautvydas ; Siksnys, Virginijus. / TnpB structure reveals minimal functional core of Cas12 nuclease family. In: Nature. 2023 ; Vol. 616, No. 7956. pp. 384-389.

Bibtex

@article{8a16817f0f784a98b67882bd88203f39,
title = "TnpB structure reveals minimal functional core of Cas12 nuclease family",
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.",
keywords = "CRISPR-Associated Proteins/chemistry, CRISPR-Cas Systems/genetics, Cryoelectron Microscopy, Deinococcus/enzymology, DNA/chemistry, DNA Transposable Elements/genetics, Endonucleases/chemistry, Evolution, Molecular, Gene Editing/methods, RNA, Guide, CRISPR-Cas Systems",
author = "Giedrius Sasnauskas and Giedre Tamulaitiene and Gytis Druteika and Arturo Carabias and Arunas Silanskas and Darius Kazlauskas and {\v C}eslovas Venclovas and Guillermo Montoya and Tautvydas Karvelis and Virginijus Siksnys",
note = "{\textcopyright} 2023. The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2023",
doi = "10.1038/s41586-023-05826-x",
language = "English",
volume = "616",
pages = "384--389",
journal = "Nature",
issn = "0028-0836",
publisher = "nature publishing group",
number = "7956",

}

RIS

TY - JOUR

T1 - TnpB structure reveals minimal functional core of Cas12 nuclease family

AU - Sasnauskas, Giedrius

AU - Tamulaitiene, Giedre

AU - Druteika, Gytis

AU - Carabias, Arturo

AU - Silanskas, Arunas

AU - Kazlauskas, Darius

AU - Venclovas, Česlovas

AU - Montoya, Guillermo

AU - Karvelis, Tautvydas

AU - Siksnys, Virginijus

N1 - © 2023. The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - CRISPR-Associated Proteins/chemistry

KW - CRISPR-Cas Systems/genetics

KW - Cryoelectron Microscopy

KW - Deinococcus/enzymology

KW - DNA/chemistry

KW - DNA Transposable Elements/genetics

KW - Endonucleases/chemistry

KW - Evolution, Molecular

KW - Gene Editing/methods

KW - RNA, Guide, CRISPR-Cas Systems

U2 - 10.1038/s41586-023-05826-x

DO - 10.1038/s41586-023-05826-x

M3 - Journal article

C2 - 37020015

VL - 616

SP - 384

EP - 389

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7956

ER -

ID: 346586911