Anyone that’s taken a high school biology class is probably familiar with the central dogma of biology—DNA is transcribed into mRNA, which is translated into protein.
As the basis for general biology, transcription and translation are fundamental to understanding the living systems scientists study. Despite the advances in technology that have made studying gene expression at the level of transcription relatively easy, translation often remains ignored. However, when cells need to rapidly respond to an environmental stressor, protein synthesis alterations are the quickest way cells can achieve that without waiting for new mRNA to be transcribed.
So how does this underappreciated fundamental aspect of biology affect human health and disease? Certain cells can utilize the rapid response mRNA translation provides to achieve protein synthesis at the right time and in the right place. This is especially useful for neurons, where the distance between cell bodies, axonal, and dendritic terminals can be substantial. For newly synthesized transcripts to travel a distance of 1 meter, the transit time is estimated at 250 hours—roughly 10 days! To solve this problem, neurons rely on rapid protein synthesis at dendritic terminals for proper synaptic function, plasticity, and memory formation. Rates of protein synthesis actually increase after learning, as demonstrated by a study measuring changes in protein synthesis in baby chicks imprinting (learning to recognize the sight and sound of their mother). By understanding how a mere visual or auditory experience directs formation of new proteins, investigators may be able to one day use sights and sounds therapeutically to help treat brain injuries.
mRNA translation also influences psychiatric disorders, including Major Depressive Disorder, which is a leading cause of disability worldwide. As a recent study reports, inhibiting phosphorylation of a key translation initiation factor, eIF4E, reprograms translation of a subset of mRNAs to enhance inflammatory responses and reduce serotonin levels. Another study also went on to demonstrate that restoring phosphorylation of eIF4E is necessary to mediate the effects of a common antidepressant.
Clearly, mRNA translation impacts neurobiology, but what about other aspects of human health? Well, on the spectrum from cancer to viral infection, translation plays a critical role in disease progression and prevention. For example, switching from cap-dependent to cap-independent translation can promote breast cancer angiogenesis and tumor survival. Mice lacking important translational repressors become obese and glucose intolerant. Viruses can shut down host protein synthesis to prevent the immune system from mounting an antiviral response. Even aging is associated with a decrease in protein synthesis. As translation is fundamental to understanding biology, it only makes sense that it plays a vital role in human health and disease. So the next time you see a discrepancy between PCR and Western blot experiments, remember that last step in the central dogma—and don’t let your work get lost in translation.
By Sadie Dierschke, Editor in Chief
Sadie is a 5th year PhD student in the BMS program. She works in the lab of Michael Dennis and is interested in understanding how early biochemical changes in the retina contribute to the pathogenesis of diabetic retinopathy.