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.
University of Oxford, Sir William Dunn School of Pathology, Oxford OX1 3RE, United Kingdom.
Marie-Joëlle
MJ
Schmidt
Steven
S
West
Chris J
CJ
Norbury
D015153:Blotting, Western; D002478:Cells, Cultured; D003593:Cytoplasm / Q000201:enzymology*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D006367:HeLa Cells; D006657:Histones / Q000235:genetics*; D006801:Humans; D047468:Immunoprecipitation; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D012313:RNA / Q000737:chemistry* / Q000235:genetics; D026721:RNA 3' End Processing / Q000502:physiology*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004268:DNA-Binding Proteins; D006657:Histones; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C511130:TUT4 protein, human; D012313:RNA