Insights into the Role of P-Bodies and Stress Granules in Protein Quality Control

Nostramo et al. identify a potential role for two novel RNA-protein granules, the P-body and stress granule, in the maintenance of normal protein homeostasis. These cytoplasmic granules are members of an ever-growing family of membraneless organelles in eukaryotic cells... The eukaryotic cell is highly compartmentalized, and contains a variety of both membrane-bound and membraneless organelles. The latter include the cytoplasmic ribonucleoprotein (RNP) granules, known as the processing body (P-body) and the stress granule. These RNP structures are thought to be involved in the storage of particular mRNAs during periods of stress. Here, we find that a mutant lacking both P-bodies and stress granules exhibits phenotypes suggesting that these structures also have a role in the maintenance of protein homeostasis. In particular, there was an increased occurrence of specific protein quality control (PQC) compartments in this mutant, an observation that is consistent with there being an elevated level of protein misfolding. These compartments normally house soluble misfolded proteins and allow the cell to sequester these polypeptides away from the remaining cellular milieu. Moreover, specific proteins that are normally targeted to both P-bodies and stress granules were found to instead associate with these PQC compartments in this granuleless mutant. This observation is interesting as our data indicate that this association occurs specifically in cells that have been subjected to an elevated level of proteotoxic stress. Altogether, the results here are consistent with P-bodies and stress granules having a role in normal protein homeostasis in eukaryotic cells.