During mammalian spermatogenesis, the mouse VASA homolog (MVH; also known as DDX4), a germ-cell-specific DEAD-box type RNA-binding protein, localizes in a germline-specific RNA granule termed the chromatoid body (CB). Genetic analyses have revealed that MVH is essential for progression through spermatogenesis, although the molecular mechanisms of its function remain elusive. We found that the acetyltransferase Hat1, and its cofactor, p46, are specifically colocalized with MVH in the CB and acetylate MVH at Lys405, leading to inactivation of its RNA-binding activity. Notably, the acetylation is developmentally regulated, paralleling the temporally regulated colocalization of Hat1 and p46 in the CB. We have identified 858 mRNAs as MVH targets, a large proportion of which correspond to previously known translationally arrested genes. Importantly, eIF4B mRNA, a target of MVH, is selectively released from the MVH-ribonucleoprotein (RNP) complex when MVH is acetylated, paralleling an increase in eIF4B protein. These findings reveal a previously unknown signaling pathway that links acetylation to RNA processing in the control of spermatogenesis.