A double-stranded RNA binding protein required for activation of repressedmessages in mammalian germ cells

Chromatin packaging in mammalian spermatozoa requires an ordered replacemen t of the somatic histones by two classes of spermatid-specific basic protei ns, the transition proteins and the protamines(1). Temporal expression of t ransition proteins and protamines during spermatid differentiation is under translational control, and premature translation of protamine 1 leads to p recocious nuclear condensation and sterility(2). We have previously suggest ed that the double-stranded (ds) RNA binding protein Prbp (encoded by the g ene Tarbp2) functions as a translational regulator during mouse spermatogen esis(3). Here we show that Prbp is required for proper translational activa tion of the mRNAs encoding the protamines. We generated mice that carry a t argeted disruption of Tarbp2 and determined that they were sterile and seve rely oligospermic. Using immunohistological analysis, we determined that th e endogenous Prm2 mRNA and a reporter mRNA carrying protamine 1 translation al-control elements were translated in a mosaic pattern. We showed that fai lure to synthesize the protamines resulted in delayed replacement of the tr ansition proteins and subsequent failure of spermiation. The timing of Prbp expression suggests that it may function as a chaperone in the assembly of specific translationally regulated ribonucleoprotein particles.