Scientists determine structure of key factor in RNA quality control

In biology, getting rid of stuff can be just as important as making it. A buildup of cells, proteins, or other molecules that are no longer needed can cause problems, so living things have evolved several ways to clean house.

A prime example is the RNA exosome. RNA molecules perform many roles in cells. Some of them are translated into proteins; others form a cell’s protein-building machinery. The RNA exosome is a cellular machine that degrades RNA molecules that are faulty, harmful, or no longer needed. Without this microscopic Marie Kondo to prune what doesn’t spark joy, our cells would become dysfunctional hoarders, unable to function.

“RNA surveillance and degradation pathways exist in all forms of life,” explains Christopher Lima, Chair of the Structural Biology Program in the Sloan Kettering Institute. “From bacteria to humans, all living things have mechanisms to monitor the quality of RNA and to purposely degrade it.”

For a long time, Dr. Lima says, these pathways were considered, like housework, kind of boring. But it turns out that these degradation pathways are highly regulated and control everything from embryonic development to the progression of the cell cycle.

What’s more, errors in these pathways can lead to many types of disease, from cancer to neurodegeneration.

In a new paper published June 9, 2022 in Cell, Dr. Lima and M. Rhyan Puno, a postdoctoral fellow in the Lima lab, present findings that help explain how the RNA exosome locates the RNA that needs to be degraded. With the help of cryogenic-electron microscopy (cryo-EM), an advanced type of imaging technology, the scientists were able to decipher the structure of a protein assembly called Nuclear Exosome Targeting (NEXT) Complex, which is a key part of the degradation machinery.

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