Journal
RNA BIOLOGY
Volume 15, Issue 4-5, Pages 594-603Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15476286.2017.1379635
Keywords
Aminoacyl-tRNA; GAAC; nutritional stress; TOR; tRNA editing
Categories
Funding
- National Science Foundation [MCB 1412611]
- Ohio State University STEP fellowship
- Ohio State University Center for RNA Biology Fellowships
- NIH [T32 GM086252]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1412611] Funding Source: National Science Foundation
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The aminoacylation status of the cellular tRNA pool regulates both general amino acid control (GAAC) and target of rapamycin (TOR) stress response pathways in yeast. Consequently, fidelity of translation at the level of aminoacyl-tRNA synthesis plays a central role in determining accuracy and sensitivity of stress responses. To investigate effects of translational quality control (QC) on cell physiology under stress conditions, phenotypic microarray analyses were used to identify changes in QC deficient cells. Nitrogen source growth assays showed QC deficient yeast grew differently compared to WT. The QC deficient strain was more tolerant to caffeine treatment than wild type through altered interactions with the TOR and GAAC pathways. Increased caffeine tolerance of the QC deficient strain was consistent with the observation that the activity of Gln3p, a transcription factor controlled by the TOR pathway, is decreased in the QC deficient strain compared to WT. GCN4 translation, which is typically repressed in the absence of nutritional stress, was enhanced in the QC deficient strain through TOR inhibition. QC did not impact cell cycle regulation; however, the chronological lifespan of QC deficient yeast strains decreased compared to wild type, likely due to translational errors and alteration of the TOR-associated regulon. These findings support the idea that changes in translational fidelity provide a mechanism of cellular adaptation by modulating TOR activity. This, in turn, supports a central role for aminoacyl-tRNA synthesis QC in the integrated stress response by maintaining the proper aa-tRNA pools necessary to coordinate the GAAC and TOR.
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