ArticleeLife2021
Molecular architecture of the human tRNA ligase complex.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 37 citations in OpenAlex.
- Ashwin and FAM98 paralogs define nuclear and cytoplasmic RNA ligase complexes for tRNA biogenesis.Nature communications · 2026Article
- Structural framework for the assembly of the human tRNA ligase complex.Nature communications · 2026Article
- DNTTIP2 coordinates RNA exosome activities to ensure fidelity of human ribosome assembly.Nature communications · 2026Article
- IVT-free, chemically synthesized protein-encoding RNA oligonucleotides for rapid production of personalized cancer vaccines.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Deciphering the impact ofGenes & diseases · 2026Article
- Inhibition of tRNA fragments dysregulated in human mTLE exacerbates pathology and seizure activity.Acta neuropathologica · 2026Article
- The ISG Atlas: a loss-of-function analysis characterizes antiviral properties of interferon stimulated genes.Nature communications · 2026Article
- The regulation, function and disease relevance of cytoplasmic tRNAs.Nature reviews. Molecular cell biology · 2026Review
- Enzymology of the metazoan tRNA ligase complex: a lifetime in cycles.Cellular and molecular life sciences : CMLS · 2026Review
- Meeting Review on India EMBO lecture course on RNA-protein complexes: from molecular assembly to physiological functions and disease.Biology open · 2026Article
- Polyglycine-mediated aggregation of FAM98B disrupts tRNA processing in GGC repeat disorders.Science (New York, N.Y.) · 2025Article
- Mechanistic basis for PYROXD1-mediated protection of the human tRNA ligase complex against oxidative inactivation.Nature structural & molecular biology · 2025Article
- TDP-43 toxic gain of function links ALS, FTD and Alzheimer's Disease through splicing dysregulation.bioRxiv : the preprint server for biology · 2025Article
- Structural and biochemical characterization of the 3'-5' tRNA splicing ligases.The Journal of biological chemistry · 2025Article
- A non-syndromic orofacial cleft risk locus links tRNA splicing defects to neural crest cell pathologies.American journal of human genetics · 2025Article
- DDX1 is required for non-spliceosomal splicing of tRNAs but not of XBP1 mRNA.Communications biology · 2025Article
- Article
- RTP801 interacts with the tRNA ligase complex and dysregulates its RNA ligase activity in Alzheimer's disease.Nucleic acids research · 2024Article
- Repair of CRISPR-guided RNA breaks enables site-specific RNA excision in human cells.Science (New York, N.Y.) · 2024Article
- Structural and mechanistic insights into activation of the human RNA ligase RTCB by Archease.Nature communications · 2024Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
RtcB enzymes are RNA ligases that play essential roles in tRNA splicing, unfolded protein response, and RNA repair. In metazoa, RtcB functions as part of a five-subunit tRNA ligase complex (tRNA-LC) along with Ddx1, Cgi-99, Fam98B, and Ashwin. The human tRNA-LC or its individual subunits have been implicated in additional cellular processes including microRNA maturation, viral replication, DNA double-strand break repair, and mRNA transport. Here, we present a biochemical analysis of the inter-subunit interactions within the human tRNA-LC along with crystal structures of the catalytic subunit RTCB and the N-terminal domain of CGI-99. We show that the core of the human tRNA-LC is assembled from RTCB and the C-terminal alpha-helical regions of DDX1, CGI-99, and FAM98B, all of which are required for complex integrity. The N-terminal domain of CGI-99 displays structural homology to calponin-homology domains, and CGI-99 and FAM98B associate via their N-terminal domains to form a stable subcomplex. The crystal structure of GMP-bound RTCB reveals divalent metal coordination geometry in the active site, providing insights into its catalytic mechanism. Collectively, these findings shed light on the molecular architecture and mechanism of the human tRNA ligase complex and provide a structural framework for understanding its functions in cellular RNA metabolism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.