Figure 1:

Liquid–liquid phase separation is the mechanism by which membrane-less organelles form. Some RNA-binding proteins with intrinsically disordered domains can undergo spontaneous LLPS in vitro. Fawzi and coworkers have shown that phase separation of the RNA-binding protein hnRNPA2 is altered by disease mutations, post-translational modifications, and protein–protein interactions. The image is a micrograph of hnRNPA2 low-complexity domain phase separation in the presence of salt and low temperature; hnRNPA2 and TDP-43 proteins aggregate together (in a test tube), providing a possible model for probing the structural details of their aggregation in neurodegenerative disease. Image credit: Veronica H. Ryan, Brown University.