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

Abstract

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 <i>Pum1</i> and <i>Pum2</i> 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 <i>Pum1/2</i>-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.