The Highly Conserved KEOPS/EKC Complex is Essential for a Universal TRNA Modification, T6A
Overview
Molecular Biology
Authors
Affiliations
The highly conserved Kinase, Endopeptidase and Other Proteins of small Size (KEOPS)/Endopeptidase-like and Kinase associated to transcribed Chromatin (EKC) protein complex has been implicated in transcription, telomere maintenance and chromosome segregation, but its exact function remains unknown. The complex consists of five proteins, Kinase-Associated Endopeptidase (Kae1), a highly conserved protein present in bacteria, archaea and eukaryotes, a kinase (Bud32) and three additional small polypeptides. We showed that the complex is required for a universal tRNA modification, threonyl carbamoyl adenosine (t6A), found in all tRNAs that pair with ANN codons in mRNA. We also showed that the bacterial ortholog of Kae1, YgjD, is required for t6A modification of Escherichia coli tRNAs. The ATPase activity of Kae1 and the kinase activity of Bud32 are required for the modification. The yeast protein Sua5 has been reported previously to be required for t6A synthesis. Using yeast extracts, we established an in vitro system for the synthesis of t6A that requires Sua5, Kae1, threonine, bicarbonate and ATP. It remains to be determined whether all reported defects of KEOPS/EKC mutants can be attributed to the lack of t6A, or whether the complex has multiple functions.
Structures of KEOPS bound to tRNA reveal functional roles of the kinase Bud32.
Ona Chuquimarca S, Beenstock J, Daou S, Porat J, Keszei A, Yin J Nat Commun. 2024; 15(1):10633.
PMID: 39639027 PMC: 11621456. DOI: 10.1038/s41467-024-54787-w.
Liu Y, Yang X, Zhou J, Yang H, Yang R, Zhu P Nat Commun. 2024; 15(1):10479.
PMID: 39622811 PMC: 11612026. DOI: 10.1038/s41467-024-54905-8.
Queuosine tRNA Modification: Connecting the Microbiome to the Translatome.
Rashad S Bioessays. 2024; 47(2):e202400213.
PMID: 39600051 PMC: 11755703. DOI: 10.1002/bies.202400213.
Wu P, Gan Q, Zhang X, Yang Y, Xiao Y, She Q mLife. 2024; 2(1):11-27.
PMID: 38818338 PMC: 10989989. DOI: 10.1002/mlf2.12051.
A highly conserved tRNA modification contributes to filamentation and virulence.
Bottcher B, Kienast S, Leufken J, Eggers C, Sharma P, Leufken C Microbiol Spectr. 2024; 12(5):e0425522.
PMID: 38587411 PMC: 11064501. DOI: 10.1128/spectrum.04255-22.