Stress granule subtypes: an emerging link to neurodegeneration

Abstract

Stress Granules (SGs) are membraneless cytoplasmic RNA granules, which contain translationally stalled mRNAs, associated translation initiation factors and multiple RNA-binding proteins (RBPs). They are formed in response to various stresses and contribute to reprogramming of cellular metabolism to aid cell survival. Because of their cytoprotective nature, association with translation regulation and cell signaling, SGs are an essential component of the integrated stress response pathway, a complex adaptive program central to stress management. Recent advances in SG biology unambiguously demonstrate that SGs are heterogeneous in their RNA and protein content leading to the idea that various SG subtypes exist. These SG variants are formed in cell type- and stress-specific manners and differ in their composition, dynamics of assembly and disassembly, and contribution to cell viability. As aberrant SG dynamics contribute to the formation of pathological persistent SGs that are implicated in neurodegenerative diseases, the biology of different SG subtypes may be directly implicated in neurodegeneration. Here, we will discuss mechanisms of SG formation, their subtypes, and potential contribution to health and disease.