Montreal Neurological Institute researcher Dr. Wayne Sossin has discovered that nerve cells can bypass the cell’s normal protein-making machinery in the same way that viruses do when they infect a cell. In a study published on-line today in Nature Neuroscience, Dr. Sossin and colleagues describe the first example of regulated IRES (internal ribosome entry site) usage after a physiological stimulus in neurons.
When a virus infects a cell, its goal is to make more virus particles. To do this, a virus takes over the cell’s protein making machinery (the ribosome), so that the cell essentially becomes a viral protein factory. It does this by using an internal ribosome entry site (IRES); which shuts down and bypasses the normal mechanisms that regulate binding of messenger RNAs to ribosomes. While many viral messenger RNAs are known to possess an IRES, few normal cellular RNAs do. Abnormal IRES regulation has been correlated with two human diseases- multiple myeloma and Charcot-Marie-Tooth disease. This is the first time that scientists have demonstrated that normal nerve cells can use an IRES to produce large quantities of protein under physiological conditions.
Dr. Sossin and colleagues made their discovery in a study of egg laying in the sea slug Aplysia. During egg laying, protein production of the egg laying hormone (ELH) increases dramatically. Sossin and colleagues discovered that the ELH messenger RNA contains an IRES. They demonstrated that after egg laying, nerve cells producing ELH switch from the normal cellular mechanism of protein production to one that uses the IRES. This switch allows for massive amounts of ELH protein to be produced at the expense of other cellular proteins, mimicking what a virus does when it infects a host cell.
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