Chemoproteomic discovery of a human RNA ligase.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36792600.
- Also identified by DOI 10.1038/s41467-023-36451-x and PMC identifier 9931718.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 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.
Medical subject headings
- RNA Ligase (ATP)
- RNA