RT Journal Article
SR Electronic
T1 Enhanced stress tolerance through reduction of G3BP and suppression of stress granules
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.02.03.925677
DO 10.1101/2020.02.03.925677
A1 Anna K. Lee
A1 Jonathon Klein
A1 Klementina Fon Tacer
A1 Tessa Lord
A1 Melissa J. Oatley
A1 Jon M. Oatley
A1 Shaina N. Porter
A1 Shondra M. Pruett-Miller
A1 Elena B. Tikhonova
A1 Andrey L. Karamyshev
A1 Peiguo Yang
A1 Hong Joo Kim
A1 J. Paul Taylor
A1 Patrick Ryan Potts
YR 2020
UL http://biorxiv.org/content/early/2020/02/04/2020.02.03.925677.abstract
AB 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.