Stress Shown to Cause Shift in Gene Products

Stress can cause a shift in gene products (mRNAs) by altered splicing, the normal cut and paste mechanism that modifies mRNA, resulting in different proteins, according to a mouse study conducted by researchers at The Hebrew University of Jerusalem (Israel) and Ben-Gurion University (Be'er Sheva, Israel). The finding was reported in the January 18, 2002, issue of Science.

The study revealed that stress causes changes in the splicing of many gene products, particularly in neurons, which has the result of modifying neuronal proteins. In particular, the ACHE gene, whose protein acetylcholinesterase helps control signaling across synapses, produces a normally rare mRNA following trauma. This mRNA produces an unusual variant of the acetylcholinesterase protein that cannot be integrated into synapses to assist transmission of nerve impulses.

The researchers measured the electrical activity in the brain of mice weeks after the mice were exposed to stress. They found much greater activity in the brains of stressed mice than in nonstressed mice. The researchers note that patients who receive drugs that affect their nervous system may eventually benefit from the recognition that stress renders them more sensitive to these drugs. The new findings suggest that altered mRNAs could be targets for a new class of drugs.

"Our study shows that stress initiates a series of events that includes changes in mRNA splicing and a consequent change of a key protein in neurons that results in an oversensitive electrical response,” said Prof. Hermona Soreq, who led the research team.




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