Polyadenylation of mRNA precursors is a two-step reaction that requires multiple protein factors. The first step, endonucleolytic cleavage of polyadenylation substrates, requires CstF (cleavage stimulation factor), a heterotrimer that is composed of three distinct subunits. CstF-64 contains an RNA binding domain and is responsible for the RNA binding activity of CstF. CstF-64 is expressed in all somatic cells and in pre- and postmeiotic, but not meiotic, germ cells. However, a large variant of CstF-64, called t CstF-64, is abundantly expressed in meiotic and postmeiotic cells in the testis and to a lesser extent in the brain, and promotes the germ cell pattern of polyadenylation. The gene encoding CstF-64 (designated CSTF2) maps to the X chromosome, whereas t CstF-64 is encoded by an autosomal gene. The increase in CstF-64 concentration during B cell activation switches IgM heavy chain mRNA expression from membrane-bound to secreted forms, suggesting that CstF-64 plays a key role in regulating IgM heavy chain expression during B cell differentiation.