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Rojas-Benitez, D., Thiaville, P.C., de Crécy-Lagard, V., Glavic, A. (2015). The Levels of a Universally Conserved tRNA Modification Regulate Cell Growth.  J. Biol. Chem. 290(30): 18699--18707.
FlyBase ID
FBrf0229116
Publication Type
Research paper
Abstract

N(6)-Threonylcarbamoyl-adenosine (t(6)A) is a universal modification occurring at position 37 in nearly all tRNAs that decode A-starting codons, including the eukaryotic initiator tRNA (tRNAi (Met)). Yeast lacking central components of the t(6)A synthesis machinery, such as Tcs3p (Kae1p) or Tcs5p (Bud32p), show slow-growth phenotypes. In the present work, we show that loss of the Drosophila tcs3 homolog also leads to a severe reduction in size and demonstrate, for the first time in a non-microbe, that Tcs3 is required for t(6)A synthesis. In Drosophila and in mammals, tRNAi (Met) is a limiting factor for cell and animal growth. We report that the t(6)A-modified form of tRNAi (Met) is the actual limiting factor. We show that changing the proportion of t(6)A-modified tRNAi (Met), by expression of an un-modifiable tRNAi (Met) or changing the levels of Tcs3, regulate target of rapamycin (TOR) kinase activity and influences cell and animal growth in vivo. These findings reveal an unprecedented relationship between the translation machinery and TOR, where translation efficiency, limited by the availability of t(6)A-modified tRNA, determines growth potential in eukaryotic cells.

PubMed ID
PubMed Central ID
PMC4513126 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Biol. Chem.
    Title
    Journal of Biological Chemistry
    Publication Year
    1905-
    ISBN/ISSN
    0021-9258
    Data From Reference