Eri1 degrades the stem-loop of oligouridylated histone mRNAs to induce replication-dependent decay

Eri1 degrades the stem-loop of oligouridylated histone mRNAs to induce replication-dependent decay
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DOI:
10.1038/nsmb.2450
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发表时间:
2013-01-01
影响因子:
16.8
通讯作者:
Heissmeyer, Vigo
Heissmeyer, Vigo
中科院分区:
生物学1区
文献类型:
--
作者:
Hoefig, Kai P.;Rath, Nicola;Heissmeyer, Vigo

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exoRNase Eri 1抑制RNA干扰并修剪5.8S rRNA 3'端。它还结合组蛋白mRNA的茎环,但这种相互作用的功能重要性仍然难以捉摸。组蛋白mRNA通常在S期结束时或在复制的药理学抑制后降解。这两个过程在Eri 1缺陷小鼠细胞中受损,而不是积累寡尿苷酸化组蛋白mRNA。Eri 1在3'端通过两个不成对的核苷酸修剪成熟的组蛋白mRNA,但在双链茎附近停止。在组蛋白mRNA的寡核苷酸化后,Lsm 1 -7异七聚体识别寡核苷酸(U)尾并与Eri 1相互作用,Eri 1的催化活性然后能够以逐步的方式降解茎环。这些数据表明,当3'寡尿苷化产生使Eri 1能够加工双链茎环结构的顺式元件时,组蛋白mRNA的降解是如何启动的。
The exoRNase Eri1 inhibits RNA interference and trims the 5.8S rRNA 3' end. It also binds to the stem-loop of histone mRNAs, but the functional importance of this interaction remains elusive. Histone mRNAs are normally degraded at the end of S phase or after pharmacological inhibition of replication. Both processes are impaired in Eri1-deficient mouse cells, which instead accumulate oligouridylated histone mRNAs. Eri1 trims the mature histone mRNAs by two unpaired nucleotides at the 3' end but stalls close to the double-stranded stem. Upon oligouridylation of the histone mRNA, the Lsm1-7 heteroheptamer recognizes the oligo(U) tail and interacts with Eri1, whose catalytic activity is then able to degrade the stem-loop in a stepwise manner. These data demonstrate how degradation of histone mRNAs is initiated when 3' oligouridylation creates a cis element that enables Eri1 to process the double-stranded stem-loop structure.