Researchers at the University of North Carolina at Chapel Hill collaborated to determine how proteins and messenger RNAs condense into liquid-like droplets within cells. The activity is a normal biological process, but it can lead to neurodegenerative diseases like Parkinson’s disease when it goes awry. The researchers found that the process is regulated by molecules of RNA that recognize each other and combine based on the very specific and complex shapes of RNA molecules.
The labs of Amy Gladfelter, associate professor of biology, and Kevin Weeks, professor of chemical biology, both in the College of Arts and Sciences at UNC-Chapel Hill, partnered on the study. Results will be published in the journal Science on April 12.
Liquid droplets form through the mixing of protein and RNA molecules. (Credit: EM Langdon et al, Science 2018)
“The inside of a cell is not random soup; it has spatial structure to it. Certain things need to be near each other, so they can work together,” said Gladfelter. “We found that the molecules of RNA are recognizing each other to join together into the same cellular droplets because of very specific and complex shapes that the RNA molecules take on.”
The findings may have implications for understanding neurodegenerative diseases like Lou Gehrig’s disease and Parkinson’s disease. Liquid droplets within cells occur under normal, healthy conditions, but through mutations, aging or stress, they can become more aggregated or harden and then they are irreversible and won’t dissolve, which is believed to cause neurodegenerative disease.
The latest findings will help researchers understand how the right components within a cell can get recruited to droplets, so that cells can potentially avoid that transition to an aberrant, solid state.
“We can’t understand what goes wrong until we develop a greater understanding of how things work and what the rules are in a ‘normal’ cell,” said Gladfelter, who is also an MBL fellow in cellular dynamics at the Marine Biological Lab in Woods Hole, Massachusetts, where some of the foundational work for the research took place.
