Feb 4, 2020

Enhanced stress tolerance through reduction of G3BP and suppression of stress granules

bioRxiv
Anna K LeePatrick Ryan Potts

Abstract

Stress granules (SG) are membrane-less ribonucleoprotein condensates that form in response to various stress stimuli via phase separation. SG act as a protective mechanism to cope with acute stress, but persistent SG have cytotoxic effects that are associated with several age-related diseases. Here, we demonstrate that the testis-specific protein, MAGE-B2, increases cellular stress tolerance by suppressing SG formation through translational inhibition of the key SG nucleator G3BP. MAGE-B2 reduces G3BP protein levels below the critical concentration for phase separation and suppresses SG initiation. Importantly, knockout of the MAGE-B2 mouse ortholog confers hypersensitivity of the male germline to heat stress in vivo. Thus, MAGE-B2 provides cytoprotection to maintain mammalian spermatogenesis, a highly thermo-sensitive process that must be preserved throughout reproductive life. These results demonstrate a mechanism that allows for tissue-specific resistance against stress through fine-tuning phase separation and could aid in the development of male fertility therapies.

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Mentioned in this Paper

Stress Granule Assembly
Stress
Spermatogenesis
G3BP1
Stress Disorders, Traumatic, Acute
Orthologous Gene
G3BP protein, human
Cytoprotection
Ribonucleoproteins
Hypersensitivity

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