Arts & Sciences

Seeking to avoid ‘full lockdown,’ cells monitor ribosome collisions

Ribosomes are the machines in the cell that use instructions from mRNA to synthesize functional proteins. There are hundreds of thousands of ribosomes in each cell, and they mostly process their instructions faithfully. But sometimes ribosomes get stuck or stall on roadblocks along defective mRNA molecules.

New research from Washington University in St. Louis shows that cells monitor for ribosome collisions to determine the severity of the problem and how best to respond when things start to go awry.

The research from the laboratory of Hani Zaher, associate professor of biology in Arts & Sciences, was published in the journal Molecular Cell.

“The cell has two methods of stress response that are triggered by this very same signal of ribosomes running into each other,” Zaher said. “However, the quality control mechanism of ribosome rescue and mRNA degradation responds more swiftly — to resolve the problems and to prevent premature activation of the integrated stress response.

“Only after cells have exhausted the capacity of the quality control system do they move to shut down the entire translation system by activating the stress response,” Zaher said.

Leo Yan, a graduate student in biology and the first author of the study, used an analogy relevant to human experience during the COVID-19 pandemic.

“Integrated stress response is like a city going through full lockdown,” Yan said. “If you only have 10 cases, you don’t want to come out and tell the city, ‘Let’s just hunker down and not do anything,’ or shut down all the productivity. You want the city to have a system to evaluate the severity of the stress — and to deal with it according to its severity.

“The value of our paper is in describing the dynamic within the system that the cell can use to evaluate the level of stress — from local, individual events, to events that require shutdown of the entire translation machinery,” he said.

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