Thiaville et al. 2016 (PRJNA292778)

General Details

Title Global Translational Impacts of the Loss of the tRNA Modification t6A in Yeast
Organism
Number of Samples 3
Release Date 2015/08/13 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP062368
ENA SRP062368
GEO GSE72030
BioProject PRJNA292778

Publication

Title
Authors Thiaville PC, Legendre R, Rojas-Benítez D, Baudin-Baillieu A, Hatin I, Chalancon G, Glavic A, Namy O, de Crécy-Lagard V
Journal Microbial cell (Graz, Austria)
Publication Date 2016 Jan 1
Abstract The universal tRNA modification t 6 A is found at position 37 of nearly all tRNAs decoding ANN codons. The absence of t 6 A 37 leads to severe growth defects in baker's yeast, phenotypes similar to those caused by defects in mcm 5 s 2 U 34 synthesis. Mutants in mcm 5 s 2 U 34 can be suppressed by overexpression of tRNA Lys UUU , but we show t 6 A phenotypes could not be suppressed by expressing any individual ANN decoding tRNA, and t 6 A and mcm 5 s 2 U are not determinants for each other's formation. Our results suggest that t 6 A deficiency, like mcm 5 s 2 U deficiency, leads to protein folding defects, and show that the absence of t 6 A led to stress sensitivities (heat, ethanol, salt) and sensitivity to TOR pathway inhibitors. Additionally, L-homoserine suppressed the slow growth phenotype seen in t 6 A-deficient strains, and proteins aggregates and Advanced Glycation End-products (AGEs) were increased in the mutants. The global consequences on translation caused by t 6 A absence were examined by ribosome profiling. Interestingly, the absence of t 6 A did not lead to global translation defects, but did increase translation initiation at upstream non-AUG codons and increased frame-shifting in specific genes. Analysis of codon occupancy rates suggests that one of the major roles of t 6 A is to homogenize the process of elongation by slowing the elongation rate at codons decoded by high abundance tRNAs and I 34 :C 3 pairs while increasing the elongation rate of rare tRNAs and G 34 :U 3 pairs. This work reveals that the consequences of t 6 A absence are complex and multilayered and has set the stage to elucidate the molecular basis of the observed phenotypes.
PMC PMC4717488
PMID 26798630
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR2157613 PRJNA292778 Saccharomyces cerevisiae 0.0 Ribo-Seq 0.0
SRR2157615 PRJNA292778 Saccharomyces cerevisiae 0.0 Ribo-Seq 0.0
SRR2157616 PRJNA292778 Saccharomyces cerevisiae 0.0 Ribo-Seq 0.0
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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