A study from Karolinska Institutet reveals how cells adapt to nutrient scarcity by altering their genetic instructions. This discovery, published in Molecular Cell, sheds light on cellular stress responses and opens up new medical treatments.
A recent study conducted at Karolinska Institutet discovered a mechanism cells use to cope with poor nutrition. When nutrients are scarce, cells make tiny shifts in how ribosomes-the cell's protein factories-read mRNA, the genetic instructions for protein production. These shifts lead to the production of aberrant proteins and accelerate the breakdown of mRNA, resulting in massive destruction of RNA that is then unavailable for protein production. This process helps cells save resources and survive tough conditions.
The research team, led by Professor Vicente Pelechano at the Department of Microbiology, Tumor and Cell Biology, found that this adaptive mechanism is conserved across bacteria, yeast, and humans.
"Our findings reveal a new way cells manage their genetic instructions under stress, which was hidden in plain sight until we applied new technologies," says Yujie Zhang , first author of the study and a postdoctoral researcher at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet.
New insights into cellular stress responses
The study utilized a special sequencing method called 5PSeq, developed at Karolinska Institutet, to observe where ribosomes are positioned on the RNA as it decays. The team integrated 5PSeq with various genomic and molecular biological methods to investigate this new mechanism.
"Understanding this mechanism provides insights into cellular stress responses and has potential therapeutic implications. For instance, regulating this process could reduce the production of aberrant proteins during aging. This new knowledge could also help us prevent bacterial and fungal cells from entering a lethargic state that helps them evade antimicrobial treatments", explains Vicent Pelechano.
The research is now focused on refining the molecular understanding of this process and exploring its therapeutic implications.
"We aim to determine how this process contributes to aging-related problems in protein production, which are highly relevant for neurodegenerative diseases. Furthermore, we are exploring whether this process can be used to make cancer cells more sensitive to immunotherapy by increasing their production of aberrant proteins that could be targeted by immunotherapy", says Vicent Pelechano
