Akademik Veri Yönetim Sistemi
BORON22, İstanbul, Türkiye, 5 - 07 Ekim 2022, cilt.1, sa.1, ss.335-337
INTRODUCTION
Boron is known as an essential micronutrient for plants and a beneficial micronutrient for animals (1,2).
Some of the biological activities it plays in plants have been revealed, but the biochemical role of boron
in animals has not been fully elucidated. While boron is required in small amounts, its excess is toxic
and the mechanism of this toxicity is unknown. Boron toxicity is not selective and affects all living
things, but different species have different susceptibility to boron. Plants living in boron-rich soils are
the most affected by boron damage, and people living in similar geographies do not experience toxicity.
Our studies include research on how excess boric acid is toxic to cells and through which biochemical
pathways it acts.
METHODS
Our studies have been carried out using yeast cells (S. cerevisiae), the most suitable cellular model, in
which genetic screenings are used cheaply and efficiently to find the pathways affected by boric acid.
Basic cellular mechanisms are distinctly conserved between yeast and other eukaryotes. Therefore,
revealing the toxicity and tolerance mechanisms using a yeast model is important in terms of guiding
the identification of similar mechanisms in humans and plants. The effects of boric acid treatment on
global gene expression, the effects of overexpression or deletion of all protein-coding genes on boron
tolerance, and proteomic analyzes were performed. In line with the information obtained, a more
detailed examination of the relevant genes and pathways was carried out.
RESULTS AND DISCUSSION
Atr1 boron efflux pump, which provides boron resistance, has been found and characterized by the
studies (3). While studying the transcriptional regulation of Atr1, it was found that it was activated by
the Gcn4 transcription factor in response to boron stress. With additional studies, it has been determined
that boron activates the general amino acid control (GAAC) mechanism and accordingly, eIF2α, one of
the translation initiation factors, is phosphated by Gcn2 kinase, thus inhibiting protein synthesis (4). In
addition, more than 30 genes determined to play a role in boron resistance and susceptibility have been
identified by yeast deletion mutant scans (4700 mutants) and proteomic methods (5). It has been
determined that there are defects related to tRNA wobble base modifications in elp1Δ, elp3Δ, elp6Δ,
ncs2Δ, ncs6Δ and kti12Δ mutants found by deletion set scans and showing resistance to boron (6). ATR1
mRNA expression levels in these mutants were significantly increased compared to wild-type cells. In
order to reveal the relationship between intracellular signal transduction and boron stress, Gcn4
interacting paths such as TOR, SNF1 and PKA pathways were analyzed. Among these, it has been
observed that especially the TOR pathway plays a role in the transmission of the intracellular boron
stress signal.
CONCLUSIONS
Understanding the molecular mechanisms of boric acid-induced toxicity is a complex phenomenon.
The data obtained from our studies show that boron creates stress similar to an amino acid shortage in
cells, and this reversibly inhibits protein synthesis via the Gcn4 pathway. The same pathway activates
the ATR1 pump protein, which throws the boric acid out of the cell, and decreases the intracellular
boron level. In this series of events, Tor1 plays a role in boron tolerance by controlling the expression
of ATR1 over Gcn4.