A role for the universal Kae1/Qri7/YgjD (COG0533) family in tRNA modification

EMBO J. 2011 Mar 2;30(5):882-93. doi: 10.1038/emboj.2010.363. Epub 2011 Feb 1.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism
  • Genetic Complementation Test
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Multiprotein Complexes
  • RNA, Transfer / chemistry*
  • RNA, Transfer / genetics
  • RNA, Transfer / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Mitochondrial Proteins
  • Multiprotein Complexes
  • Qri7 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • N(6)-(N-threonylcarbonyl)adenosine
  • RNA, Transfer
  • Kae1 protein, S cerevisiae
  • Metalloendopeptidases
  • Adenosine