Dreaming of a scenario where our understanding of one of the most basic aspects of cellular life (nutritional sensing and growth regulation) is in our mind. This is exactly about the target of the rapamycin (Tor) complex, a target of the key protein complex in the cell. This complex, long considered an unwavering role under glucose starvation conditions. meaning? The seismic shift in our understanding of cellular adaptation has potentially far-reaching implications for the field from agriculture to medicine. This exciting new study reveals that TOR inactivation is not only a simple switch, but also triggers a series of changes that lead to the formation of heterochromatin in RDNA. Stay tuned as we dig deep into the complex dance of cellular responses not only reactions, but adaptation and survival.
In a key discovery, co-led researchers Dr. Hayato Hirai and Professor Kunihiro Ohta, along with team members Ms. Yuki Sen, Ms. Miki Tamura of the University of Tokyo, and Ms. Miki Tamura of Miki Tamura, revealed the complex mechanisms of genetic regulation during nutritional yeast fear. Their study, published in the Cell Report, examines the complex interactions of cell responses in a type of fission yeast under the conditions of nutritional deficiency. This study elucidates new aspects of gene regulation, especially focusing on how cells respond to environmental stress in response to ribosomal gene expression. The team’s findings suggest that the unique process of histone modification and heterochromatin formation distinguishes it from known mechanisms in other yeasts, such as Saccharomyces cerevisiae.
Dr. Hayato Hirai elucidates the essence of their discovery: “Nutrition depletion inactivates the TOR pathway, leading to a sluggish ribosomal gene expression.” This mechanism involves the deactivation of Tolk1 in the rDNA region, which plays a key role in controlling gene expression associated with ribosome production. Dissociation of ATF1, stress-reactive transcription factors, and factual accumulation, is a histone chaperone that helps maintain H3K9 methylation and subsequent heterochromatin formation, thereby facilitating this process.
Professor Kunihiro Ohta stressed the importance of its approach, highlighting the intricate links in cellular regulation: “The TOR pathway may be an upstream regulator of the ATF1, FACT and RNAI pathways in S. Pombe”. This insight shows that in response to environmental cues, a network of complex regulatory pathways is carried out when it comes to its function.
The team adopted various innovative technologies, such as CHIP-QPCR, targeting H3K9 methylation, a marker of heterochromatin formation. Dr. Hirai stressed: “Our CHIP-QPCR results show that the increase in H3K9ME2 levels in TORC1-inactivated cells suggests a direct effect of TORC1-inactivated on heterochromatin formation.”
Their discovery opens new avenues to understand how cells preserve energy and regulate growth under nutrient-limited conditions. Professor Ohta added: “This regulation of ribosomal gene expression is crucial for cell viability during nutrient scarcity.”
In addition to yeast, this study has potential implications for understanding similar pathways in higher organisms, including humans. “The mechanisms we find in fission yeast may have similarities in more complex eukaryotes, thus providing new insights into the response of human cells to environmental stress,” Dr. Hirai suggested.
All in all, the research of Dr. Hirai, Professor Ohta and his team marks an important step in our understanding of the honeycomb response to cellular deprivation. It not only adds a new dimension to our knowledge of gene regulation in fission yeast, but also paves the way for exploring similar pathways in more complex organisms.
Journal Reference
Hayato Hirai, Yuki Sen, Miki Tamura, Kunihiro Ohta. “Inactivation triggers heterochromatin formation in rDNA during glucose starvation.” Cell Report, 2023. Doi:
