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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.

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