Journal
NUCLEIC ACIDS RESEARCH
Volume 45, Issue 2, Pages 805-817Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkw1181
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Funding
- Canadian Institutes of Health Research (CIHR) Foundation [FDN 143277, FDN 143343, FDN 143301]
- Genome Canada and Ontario Genomics Funding [OGI-088]
- CIHR Foundation [FDN 143277]
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The KEOPS/EKC complex is a tRNA modification complex involved in the biosynthesis of N-6-threonylcarbamoyladenosine (t(6)A), a universally conserved tRNA modification found on ANN-codon recognizing tRNAs. In archaea and eukaryotes, KEOPS is composed of OSGEP/Kae1, PRPK/Bud32, TPRKB/Cgi121 and LAGE3/Pcc1. In fungi, KEOPS contains an additional subunit, Gon7, whose orthologs outside of fungi, if existent, remain unidentified. In addition to displaying defective t(6)A biosynthesis, Saccharomyces cerevisiae strains harboring KEOPS mutations are compromised for telomere homeostasis, growth and transcriptional coactivation. To identify a Gon7 ortholog in multicellular eukaryotes as well as to uncover KEOPSinteracting proteins that may link t(6)A biosynthesis to the diverse set of KEOPS mutant phenotypes, we conducted a proteomic analysis of human KEOPS. This work identified 152 protein interactors, one of which, C14ORF142, interacted strongly with all four KEOPS subunits, suggesting that it may be a core component of human KEOPS. Further characterization of C14ORF142 revealed that it shared a number of biophysical and biochemical features with fungal Gon7, suggesting that C14ORF142 is the human ortholog of Gon7. In addition, our proteomic analysis identified specific interactors for different KEOPS subcomplexes, hinting that individual KEOPS sub-units may have additional functions outside of t(6)A biosynthesis.
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