Faculty, Staff and Student Publications
Language
English
Publication Date
10-15-2024
Journal
Proceedings of the National Academy of Sciences of the United States of America
DOI
10.1073/pnas.2408249121
PMID
39388274
PMCID
PMC11494293
PubMedCentral® Posted Date
10-10-2024
PubMedCentral® Full Text Version
Post-print
Abstract
ATP-grasp superfamily enzymes contain a hand-like ATP-binding fold and catalyze a variety of reactions using a similar catalytic mechanism. More than 30 protein families are categorized in this superfamily, and they are involved in a plethora of cellular processes and human diseases. Here, we identify C12orf29 (RLIG1) as an atypical ATP-grasp enzyme that ligates RNA. Human RLIG1 and its homologs autoadenylate on an active site Lys residue as part of a reaction intermediate that specifically ligates RNA halves containing a 5’-phosphate and a 3’-hydroxyl. RLIG1 binds tRNA in cells and can ligate tRNA within the anticodon loop in vitro. Transcriptomic analyses of Rlig1 knockout mice revealed significant alterations in global tRNA levels in the brains of female mice, but not in those of male mice. Furthermore, crystal structures of a RLIG1 homolog from Yasminevirus bound to nucleotides revealed a minimal and atypical RNA ligase fold with a conserved active site architecture that participates in catalysis. Collectively, our results identify RLIG1 as an RNA ligase and suggest its involvement in tRNA biology.
Keywords
Animals, RNA, Transfer, Mice, RNA Ligase (ATP), Humans, Catalytic Domain, Mice, Knockout, Female, Male, Crystallography, X-Ray, Models, Molecular, C12orf29, RNA ligase, tRNA, RLIG1
Published Open-Access
yes
Recommended Citation
Hu, Yingjie; Lopez, Victor A; Xu, Hengyi; et al., "Biochemical and Structural Insights Into a 5′ to 3′ RNA Ligase Reveal a Potential Role in tRNA Ligation" (2024). Faculty, Staff and Student Publications. 6748.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6748
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