BOULE is Essential for the Dynamic Disassembly of Heat Shock Granules in Male Germ Cells

ABSTRACT Heat shock triggers stress granule (SG) formation, yet their dynamics in mammalian germ cells remain unclear. Through systematic analysis, we uncovered distinct heat shock granule (HSG) composition and stage‐specific assembly/disassembly in the mouse testis. Ribosome profiling revealed that germ cells selectively sustain translation of spermatogenic genes during heat shock. We identified that the germ cell‐specific RNA‐binding protein BOULE is essential for HSG clearance. BOULE deficiency under heat shock impairs HSG disassembly, with increased germ cell apoptosis and a disrupted ubiquitinome. Mechanistically, BOULE orchestrates HSG clearance through a two‐pronged mechanism. It post‐transcriptionally maintains the expression of the disassembly factors G3BP1 and FAF2. Additionally, BOULE promotes heat‐shock‐induced ubiquitination of G3BP1 by regulating the E3 ligase TRIM27, thereby recruiting the VCP/FAF2 complex. Our findings establish BOULE as a key regulator of proteostasis that coordinates HSG disassembly in germ cells, providing mechanistic insight into heat shock‐induced germ cell damage that may contribute to male infertility.