ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
BOULE is Essential for the Dynamic Disassembly of Heat Shock Granules in Male Germ Cells.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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.
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