The human cytoplasmic RNA terminal U-transferase ZCCHC11 targets histone mRNAs for degradation.

Inhibition of eukaryotic DNA replication leads to the rapid suppression of histone synthesis, via 3' uridylation of cytoplasmic histone mRNAs followed by their Lsm1-7-mediated decapping and degradation. Here we show that the human cytoplasmic RNA terminal U-transferase ZCCHC11, recently implicated in microRNA metabolism, associates with replication-dependent histone mRNAs. Knockdown of ZCCHC11 selectively blocked histone mRNA degradation following inhibition of DNA replication, whereas knockdown of PAPD1 or PAPD5, previously proposed as candidate histone mRNA U-transferases, had no such effect. Furthermore, a reduction in the proportion of histone transcripts that were uridylated was observed following ZCCHC11 knockdown. Our data indicate that ZCCHC11 is the terminal U-transferase responsible for targeting human histone mRNAs for degradation following inhibition or completion of DNA replication.

Polyadenylation and beyond: emerging roles for noncanonical poly(A) polymerases.

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.