Response to stress in biological disorders: Implications of stress granule assembly and function

Abstract

It is indispensable for cells to adapt and respond to environmental stresses, in order for organisms to survive. Stress granules (SGs) are condensed membrane‐less organelles dynamically formed in the cytoplasm of eukaryotes cells to cope with diverse intracellular or extracellular stress factors, with features of liquid‐liquid phase separation. They are composed of multiple constituents, including translationally stalled mRNAs, translation initiation factors, RNA‐binding proteins and also non‐RNA‐binding proteins. SG formation is triggered by stress stimuli, viral infection and signal transduction, while aberrant assembly of SGs may contribute to tissue degenerative diseases. Recently, a growing body of evidence has emerged on SG response mechanisms for cells facing high temperatures, oxidative stress and osmotic stress. In this review, we aim to summarize factors affecting SGs assembly, present the impact of SGs on germ cell development and other biological processes. We particularly emphasize the significance of recently reported RNA modifications in SG stress responses. In parallel, we also review all current perspectives on the roles of SGs in male germ cells, with a particular focus on the dynamics of SG assembly.

Abstract

Schematic illustration for heat stress in male germ cells. Heat stress induces stress granule (SG) formation by phosphorylating eIF2α, recruiting RNA binding protein (DAZL, BOULE, RACK, MAGE‐B2) and ultimately protecting normal spermatogenesis from germ cell apoptosis. eIF2α (eukaryotic initiation factor‐2alpha), MAPK (mitogen‐activated protein kinases), DAZL (deleted in azoospermia‐like), BOULE (a founding member of the DAZ gene family), RACK (receptor for activated protein kinase C), MAGE‐B2 (testis‐specific protein)