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Chemoproteomic discovery of a human RNA ligase.

ABSTRACT: 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.

SUBMITTER: Yuan Y

PROVIDER: S-EPMC9931718 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Chemoproteomic discovery of a human RNA ligase.

Yuan Yizhi Y Stumpf Florian M FM Schlor Lisa A LA Schmidt Olivia P OP Saumer Philip P Huber Luisa B LB Frese Matthias M Höllmüller Eva E Scheffner Martin M Stengel Florian F Diederichs Kay K Marx Andreas A

Nature communications 20230215 1

RNA ligases are present across all forms of life. While enzymatic RNA ligation between 5'-PO<sub>4</sub> 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'-PO<sub>4</sub> and ...[more]

PMID: 36792600

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Chemoproteomic discovery of a human RNA ligase

Project description: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 the first 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. This data provides the groundwork for establishing a human RNA repair pathway.

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