title: A role for the universal Kae1/Qri7/YgjD (COG0533) family in tRNA modification.
abstract: The YgjD/Kae1 family (COG0533) has been on the top-10 list of universally conserved proteins of unknown function for over 5 years. It has been linked to DNA maintenance in bacteria and mitochondria and transcription regulation and telomere homeostasis in eukaryotes, but its actual function has never been found. Based on a comparative genomic and structural analysis, we predicted this family was involved in the biosynthesis of N(6)-threonylcarbamoyl adenosine, a universal modification found at position 37 of tRNAs decoding ANN codons. This was confirmed as a yeast mutant lacking Kae1 is devoid of t(6)A. t(6)A(-) strains were also used to reveal that t(6)A has a critical role in initiation codon restriction to AUG and in restricting frameshifting at tandem ANN codons. We also showed that YaeZ, a YgjD paralog, is required for YgjD function in vivo in bacteria. This work lays the foundation for understanding the pleiotropic role of this universal protein family.
authors.affiliation: Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA. basma@ufl.edu.edu
authors.forename: Basma
authors.initials: B
authors.lastname: El Yacoubi
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hatin
authors.forename: Christopher
authors.initials: C
authors.lastname: Deutsch
authors.forename: Tamer
authors.initials: T
authors.lastname: Kahveci
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Rousset
authors.forename: Dirk
authors.initials: D
authors.lastname: Iwata-Reuyl
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Murzin
authors.forename: Valérie
authors.initials: V
authors.lastname: de Crécy-Lagard
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005816:Genetic Complementation Test; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes; D012343:RNA, Transfer / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D046912:Multiprotein Complexes; C544825:Qri7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C003268:N(6)-(N-threonylcarbonyl)adenosine; D012343:RNA, Transfer; C480738:Kae1 protein, S cerevisiae; D008666:Metalloendopeptidases; D000241:Adenosine