Each cell has their own genetic code that helps maintain viability and directs function. This genetic code is commonly referred to as deoxyribonucleic acid or DNA. DNA is the molecule that carries genetic instructions that dictate the development and function of each living cell within an organism. Another form of genetic material that is critical for the survival of multicellular organisms includes ribonucleic acid (RNA). This molecule is critical in carrying out protein production dictated by gene expression. Unlike DNA, RNA is single stranded and used as a template to encode for protein structures. As a result, these proteins maintain normal function in cells and aid in cell response from outside stimuli.
In various pathologies, cells become dysregulated and either stop functioning or adapt by altering their activity. Outside stimuli can lead to cell stress or a disruption in the cell’s normal environment with the potential of damaging cell structure. Cell damage can be a result of a variety of factors including internal/external injury, stress induction, or damage repair. In response to counteract stress, cells will employ various mechanisms to repair proteins or pathways that were previously injured. Consequently, if the stress-induced damage is too great, cells will die through a process call ‘apoptosis’. Recent findings have implicated RNA, specifically messenger (mRNA), in influencing cell stress response. Messenger RNA is responsible for carrying genetic material to produce proteins and is identified by the marker m6A. An increase of m6A is found on mRNA that encodes for proteins associated with cell survival and other stress response pathways. In a healthy cell, m6A will breakdown stress-reactive mRNAs to maintain low stress responses.
In a recent article published in Cell, by Dr. Samie Jaffrey and others, demonstrated the mechanism by which m6A leads to the disposal of mRNA. Specifically, how m6A triggers disposal of mRNA as it is used as a template to create proteins. Jaffrey is the Greenberg-Starr Professor within the Department of Pharmacology at Weill Cornell Medicine. His work investigates the regulation of mRNA and its stability to impact gene express in healthy and disease tissues. His work has led to the conclusion that RNA dysregulation can lead to neurological dysfunction, cancer, and others.
The team discovered that m6A is detected by a protein called a ribosome. Ribosomes ensure high m6A expressing RNA are degraded to avoid increased in cell stress response proteins. However, when the cell is stressed, this disposal process is stalled as the ribosome protein stops degradation when it encounters m6A. Once the degradation process stops, mRNAs accumulate and create more proteins to help cells recover from stress.
These findings help explain foundational questions about m6A and implicate how it can be targeted in future immunotherapy developments. It also helps shift our understanding of m6A and how this marker can be naturally triggered to control cell physiology. Overall, the work done by Jaffrey and others improves our knowledge of cell stress response and has the potential to improve cellular therapies to aid in cancer treatment.
