Department of Chemistry, University of Konstanz, Universitätsstraße 10, 78457, Konstanz, Germany.
Konstanz Research School Chemical Biology, University of Konstanz, Universitätsstraße 10, 78457, Konstanz, Germany.
Nat Commun. 2023 Feb 15;14(1):842. doi: 10.1038/s41467-023-36451-x.
RNA ligases are present across all forms of life. While enzymatic RNA ligation between 5'-PO 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 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.
RNA 连接酶存在于所有生命形式中。虽然在病毒、真菌和植物中，5'-PO 和 3'-OH 末端之间的酶促 RNA 连接很常见，但在脊椎动物中尚未发现这种 RNA 连接酶。在这里，我们使用了一种基于核苷酸的化学探针，靶向人类 AMP 化蛋白质组，我们已经富集并鉴定了迄今为止尚未表征的人类蛋白质染色体 12 开放阅读框 29（C12orf29）作为一种促进 5'-PO 和 3'-OH 末端之间 RNA 连接的人类酶。C12orf29 通过三步机制催化 ATP 依赖性 RNA 连接，涉及串联自动和 RNA AMP 化。C12ORF29 基因的敲除会阻碍细胞对氧化应激的恢复能力，同时伴随着 RNA 降解，这表明 C12orf29 在维持 RNA 完整性方面发挥作用。这些数据为建立人类 RNA 修复途径奠定了基础。
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