The Catalytic Activity of the Ubp3 Deubiquitinating Protease Is Required for Efficient Stress Granule Assembly in Saccharomyces cerevisiae.

The interior of the eukaryotic cell is a highly compartmentalized space containing both membrane-bound organelles and the recently identified nonmembranous ribonucleoprotein (RNP) granules. This study examines in Saccharomyces cerevisiae the assembly of one conserved type of the latter compartment, known as the stress granule. Stress granules form in response to particular environmental cues and have been linked to a variety of human diseases, including amyotrophic lateral sclerosis. To further our understanding of these structures, a candidate genetic screen was employed to identify regulators of stress granule assembly in quiescent cells. These studies identified a ubiquitin-specific protease, Ubp3, as having an essential role in the assembly of these RNP granules. This function was not shared by other members of the Ubp protease family and required Ubp3 catalytic activity as well as its interaction with the cofactor Bre5. Interestingly, the loss of stress granules was correlated with a decrease in the long-term survival of stationary-phase cells. This phenotype is similar to that observed in mutants defective for the formation of a related RNP complex, the Processing body. Altogether, these observations raise the interesting possibility of a general role for these types of cytoplasmic RNP granules in the survival of G0-like resting cells.