Journal
JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
Volume 79, Issue -, Pages -Publisher
ELSEVIER GMBH
DOI: 10.1016/j.jtemb.2023.127222
Keywords
Boric acid; Boron stress; Yeast; General amino acid control; Tor pathway; Gcn1
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Although boron is essential for many organisms, excessive amounts can cause toxicity. The mechanism behind this toxicity is not fully understood yet. The Gcn4 transcription factor plays a crucial role in the boron stress response. Various transcription factors and cell signaling pathways regulate the Gcn4 transcription factor, but it is unknown how boron signaling is mediated to Gcn4. Our study using yeast as a model reveals that the GCN system is activated by uncharged tRNA stress in response to boron treatment. The TOR pathway is necessary for a proper response against boric acid stress.
Although boron is an essential element for many organisms, an excess amount of it can cause toxicity, and the mechanism behind this toxicity is not yet fully understood. The Gcn4 transcription factor plays a crucial role in the boron stress response by directly activating the expression of the boron efflux pump Atr1. More than a dozen transcription factors and multiple cell signaling pathways have roles in regulating the Gcn4 transcription factor under various circumstances. However, it is unknown which pathways or factors mediate boron signaling to Gcn4. Using the yeast Saccharomyces cerevisiae as a model, we analyzed the factors that converge on the Gcn4 transcription factor to assess their possible roles in boron stress signaling. Our findings show that the GCN system is activated by uncharged tRNA stress in response to boron treatment and that GCN1, which plays a role in transferring uncharged tRNAs to Gcn2, is necessary for the kinase activity of Gcn2. The SNF and PKA pathways were not involved in mediating boron stress, even though they interact with Gcn4. Mutations in TOR pathway genes, such as GLN3 and TOR1, abolished Gcn4 and ATR1 activation in response to boric acid treatment. Therefore, our study suggests that the TOR pathway must be functional to form a proper response against boric acid stress.
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