PUM1 and PUM2 promote translation of chromatin regulators to ensure mammalian spermatogenesis.

Translational control is essential for male germ cell development, yet how post-transcriptional regulation is coupled to chromatin remodeling during spermatogenesis remains poorly understood. Here, we show that the RNA-binding proteins PUMILIO1 (PUM1) and PUMILIO2 (PUM2) promote translation of mRNAs encoding chromatin regulators in the mouse testis. Conditional deletion of Pum1 and Pum2 in germ cells at multiple developmental stages results in spermatogenic failure, defective nuclear shaping, impaired histone-to-protamine exchange, and complete male sterility. Polysome profiling and ribosome sequencing reveal selective reductions in translation efficiency of chromatin regulators, including histone modifiers and nucleosome remodelers, in Pum1/2-deficient testes. Mechanistically, PUM1/2 associate with DAZL and PABPC1 to form a germ cell-specific translational activation complex that enhances protein output with little impact on mRNA stability. Together, these findings redefine mammalian PUM proteins as context-dependent translational activators in the germline and uncover a post-transcriptional mechanism that links RNA regulation to chromatin dynamics during spermatogenesis.