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

The human cytoplasmic RNA terminal U-transferase ZCCHC11 targets histone mRNAs for degradation
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DOI:
10.1261/rna.2252511
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发表时间:
2011-01-01
期刊:
RNA
影响因子:
4.5
通讯作者:
Norbury, Chris J.
Norbury, Chris J.
中科院分区:
生物学3区
文献类型:
--
作者:
Schmidt, Marie-Joelle;West, Steven;Norbury, Chris J.

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真核DNA复制的抑制导致组蛋白合成的快速抑制,通过胞质组蛋白mRNA的尿苷化,随后是它们的Lsm 1 -7介导的脱帽和降解。在这里,我们表明,人类细胞质RNA末端U-转移酶ZCCHC 11,最近牵连在microRNA代谢,与复制依赖性组蛋白mRNA。ZCCHC 11的敲除选择性地阻断了DNA复制抑制后的组蛋白mRNA降解,而先前被提出作为候选组蛋白mRNA U-转移酶的PAPD 1或PAPD 5的敲除则没有这种作用。此外,在ZCCHC 11敲低后观察到组蛋白转录物被尿苷化的比例降低。我们的数据表明,ZCCHC 11是负责靶向人类组蛋白mRNA的末端U-转移酶,用于在抑制或完成DNA复制后降解。
Inhibition of eukaryotic DNA replication leads to the rapid suppression of histone synthesis, via 39 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.