Like a droplet of oil in water, phase separation helps proteins and RNA in cells come together. This process is highly regulated and specific.
St. Jude scientists are studying how phase separation forms structures called stress granules. Stress granules in the lab are comparable to structures in human neurons that are involved in diseases like amyotrophic lateral sclerosis, which is also called Lou Gehrig’s disease.
The team found that phase separation is controlled by a network of interactions between proteins and RNA. By studying the interactions, the researchers determined how each protein contributes.
“The parts of the stress granule interact, but they don’t interact with each other equally,” said senior author J. Paul Taylor, MD, PhD, St. Jude Department of Cell and Molecular Biology chair. “Individual proteins play different roles, some more important than others.”
Their findings show that the most important nodes in the network drive phase separation. For stress granules, the central node is a protein called G3BP1.
Intrinsically disordered proteins are notable for their lack of structure. The interplay between three distinct intrinsically disordered regions in G3BP1 fine-tunes its ability to phase separate.
Cell published a report on this work.