Researchers have found that messenger RNA (mRNA) and a protein called ZAK are crucial in the cell’s response to UV radiation damage, determining whether the cell survives or dies.
UV radiation can harm DNA, but it can also damage mRNA, which acts as an initial responder to cellular stress. This discovery, published in Cell on June 5, reveals that mRNAs play a pivotal role in instructing cells on how to cope with UV radiation damage.
Rachel Green, Ph.D., from Johns Hopkins University School of Medicine, explains that RNA serves as an early indicator of significant damage, signaling to the cell the need for action. Green, the lead author of the study, describes how ZAK detects cellular damage by monitoring ribosomes’ movements along UV-damaged mRNAs, leading to a cascade of events that determine the cell’s fate.
Understanding how cells respond to UV radiation can provide insights into the development of skin cancer and other malignancies. Drugs targeting ribosomes may benefit from targeting ZAK to induce cell death in various cancer types.
The study highlights that ZAK’s response is proportional to the level of cellular damage caused by UV radiation. This nuanced understanding could lead to novel strategies to regulate ZAK’s activity effectively.
According to Green, ZAK signaling and ribosome collisions are the primary factors influencing a skin cell’s fate following UV exposure, overshadowing the role of DNA damage and its repair mechanisms.
The research, co-led by Sergi Regot, Ph.D., and Alban Ordureau, Ph.D., involved exposing human cellular models to UV radiation and analyzing ZAK’s role in cell signaling. Live cell imaging experiments and ribosome biochemistry experiments shed light on how ZAK-mediated responses govern cell death in UV-irradiated cells.
Future investigations will focus on different cell types, particularly fast-growing cells like those in melanoma, to determine the extent of ZAK’s impact on regulating cell survival.
Funding for this research was provided by various institutions, including the Howard Hughes Medical Institute, the National Institutes of Health, and the National Science Foundation.
