Regulation of translation by stress granules and processing bodies

Abstract

Stress necessitates rapid reprogramming of translation in order to facilitate an adaptive response and promote survival. Cytoplasmic stress granules (SGs) and processing bodies (PBs) are dynamic structures that form in response to stress-induced translational arrest. PBs are linked to mRNA silencing and decay, while SGs are more closely linked to translation and the sorting of specific mRNAs for different fates. While they share some components and can interact physically, SGs and PBs are regulated independently, house separate functions, and contain unique markers. SG formation is associated with numerous disease states, and the expanding list of SG-associated proteins integrates SG formation with other processes such as transcription, splicing, and survival. Growing evidence suggests that SG assembly is initiated by translational arrest, and mediates cross talk with many other signaling pathways.

Fig. 1

Model depicting the graded stages of SG assembly. Stalled initiation allows elongating ribosomes to leave polysomes, resulting in stalled 48S mRNPs which recruit available cytoplasmic RNA-binding proteins (blue region), many of which would normally shuttle into the nucleus (pink area). Locally high concentrations of mRNPs promote aggregation into small complexes, which progressively fuse into larger aggregates, assisted by microtubule-dependent motors. Sorting ensues as the higher affinity interactions prevail, and as other signaling molecules are recruited. Subsets of mRNPs may be removed from the SGs pending phosphorylation and 14-3-3 binding and shunted to PBs for decay (e.g., TTP). Other mRNPs may be exported for other fates.