The addition of nontemplated nucleotides, particularly adenylyl and uridylyl residues, to the 3′ ends of RNA substrates has been the focus of much attention in recent years, and these studies have generated some intriguing surprises. In addition to the well-known canonical poly(A) polymerase (PAP) that polyadenylates mRNAs prior to export from the nucleus to the cytoplasm, a separate class of noncanonical poly(A) polymerases has emerged over the past decade. Studies on various organisms have led to the realization that these noncanonical PAPs, which are conserved from yeast to mammals, play crucial and diverse roles in the regulation of gene expression. Here we review the current knowledge of these enzymes, with an emphasis on the human proteins, and highlight recent discoveries that have implications far beyond the understanding of RNA metabolism itself. Copyright © 2010 John Wiley & Sons, Ltd.
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