Reexamining the polyadenylation signal: were we wrong about AAUAAA?

Polyadenylation is the process by which most eukaryotic mRNAs form their 3' ends. It was long held that polyadenylation required the sequence AAUAAA and that 90% of mRNAs had AAUAAA within 30 nucleotides of the site of poly(A) addition. More recent studies, aided by computer analysis of sequences made available in GenBank and expressed sequence tag (EST) databases, have suggested that the actual incidence of AAUAAA is much lower, perhaps as low as 50-60%. Reproductive biologists have long recognized that a large number of mRNAs in male germ cells of mammals lack AAUAAA but are otherwise normally polyadenylated. Recent research in our laboratory has uncovered a new form of an essential polyadenylation protein, tauCstF-64, that is most highly expressed in male germ cells, and to a smaller extent in the brain, and which we propose plays a significant role in AAUAAA-independent mRNA polyadenylation in germ cells.