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Chemoproteomic discovery of a human RNA ligase

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2023

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European Union (EU): 101019280

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Nature Communications. Nature Publishing Group. 2023, 14, 842. eISSN 2041-1723. Available under: doi: 10.1038/s41467-023-36451-x

Zusammenfassung

RNA ligases are present across all forms of life. While enzymatic RNA ligation between 5′-PO4 and 3′-OH termini is prevalent in viruses, fungi, and plants, such RNA ligases are yet to be identified in vertebrates. Here, using a nucleotide-based chemical probe targeting human AMPylated proteome, we have enriched and identified the hitherto uncharacterised human protein chromosome 12 open reading frame 29 (C12orf29) as a human enzyme promoting RNA ligation between 5′-PO4 and 3′-OH termini. C12orf29 catalyses ATP-dependent RNA ligation via a three-step mechanism, involving tandem auto- and RNA AMPylation. Knock-out of C12ORF29 gene impedes the cellular resilience to oxidative stress featuring concurrent RNA degradation, which suggests a role of C12orf29 in maintaining RNA integrity. These data provide the groundwork for establishing a human RNA repair pathway.

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570 Biowissenschaften, Biologie

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ISO 690YUAN, Yizhi, Florian M. STUMPF, Olivia SCHMIDT, Philip SAUMER, Luisa B. HUBER, Matthias FRESE, Eva HÖLLMÜLLER, Martin SCHEFFNER, Florian STENGEL, Kay DIEDERICHS, Andreas MARX, 2023. Chemoproteomic discovery of a human RNA ligase. In: Nature Communications. Nature Publishing Group. 2023, 14, 842. eISSN 2041-1723. Available under: doi: 10.1038/s41467-023-36451-x
BibTex
@article{Yuan2023Chemo-66124,
  year={2023},
  doi={10.1038/s41467-023-36451-x},
  title={Chemoproteomic discovery of a human RNA ligase},
  volume={14},
  journal={Nature Communications},
  author={Yuan, Yizhi and Stumpf, Florian M. and Schmidt, Olivia and Saumer, Philip and Huber, Luisa B. and Frese, Matthias and Höllmüller, Eva and Scheffner, Martin and Stengel, Florian and Diederichs, Kay and Marx, Andreas},
  note={F.S. acknowledges the Deutsche Forschungsgemeinschaft for funding (STE 2517/5-1) Article Number: 842}
}
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F.S. acknowledges the Deutsche Forschungsgemeinschaft for funding (STE 2517/5-1)
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