The Levels of a Universally Conserved tRNA Modification Regulate Cell GrowthReportar como inadecuado

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N-6-Threonylcarbamoyl-adenosine t6A is a universal modification occurring at position 37 in nearly all tRNAs that decode A-starting codons, including the eukaryotic initiator tRNA tRNAiMet. Yeast lacking central components of the t6A 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 t6A synthesis. In Drosophila and in mammals, tRNAiMet is a limiting factor for cell and animal growth. We report that the t6A-modified form of tRNAiMet is the actual limiting factor. We show that changing the proportion of t6A-modified tRNAiMet, by expression of an un-modifiable tRNAiMet 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 t6A-modified tRNA, determines growth potential in eukaryotic cells.Nota general

Artículo de publicación ISI

Autor: Rojas Benítez, Diego; - Thiaville, Patrick C.; - Crécy-Lagard, Valérie de; - Glavic Maurer, Alvaro; -



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