Chemoproteomic discovery of a human RNA ligase.
Yizhi YuanFlorian M StumpfLisa A SchlorOlivia P SchmidtPhilip SaumerLuisa B HuberMatthias FreseEva HöllmüllerMartin ScheffnerFlorian StengelKay DiederichsAndreas MarxPublished in: Nature communications (2023)
RNA ligases are present across all forms of life. While enzymatic RNA ligation between 5'-PO 4 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 4 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.
Keyphrases
- endothelial cells
- nucleic acid
- oxidative stress
- pluripotent stem cells
- squamous cell carcinoma
- gene expression
- minimally invasive
- depressive symptoms
- nitric oxide
- dna methylation
- dna damage
- machine learning
- genome wide
- drug delivery
- working memory
- hydrogen peroxide
- binding protein
- ischemia reperfusion injury
- artificial intelligence
- transcription factor
- amino acid
- locally advanced
- diabetic rats
- heat shock
- heat shock protein