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 of 77, 64 and 50 kDa. Heterotrimeric CstF recognizes GU and U-rich sequences located downstream of the polyadenylation site on RNA. The 50 kDa CstF subunit shares extensive homology with mammalian G protein beta-subunits and has a transducin repeat domain, which is a 44 amino acid-long sequence that is repeated seven times. CstF-50 interacts with the nuclear protein BARD1 (BRCA1-associated RING domain protein) and inhibits polyadenylation in vitro. CstF-50 may also be responsible for the interaction of the heterotrimeric CstF complex with other polyadenylation and 3'-end cleavage factors to form a stable complex on the pre-mRNA.