Polysomal ribonuclease 1 exists in a latent form on polysomes prior to estrogen activation of mRNA decoy
Polysomal ribonuclease 1 exists in a latent form on polysomes prior to estrogen activation of mRNA decoy
复制标题
DOI：
10.1093/nar/29.5.1156
复制
发表时间：
2001-03-01
影响因子：
14.9
通讯作者：
Schoenberg, DR
中科院分区：
文献类型：
--
作者：
Cunningham, KS;Hanson, MN;Schoenberg, DR
雌激素导致非洲爪哇肝细胞翻译图谱的全球变化，以卵黄蛋白前体卵黄蛋白原的产生取代血清蛋白质的合成。这是通过血清蛋白mRNAs的协调失稳和卵黄蛋白原mRNA的转录诱导和随后的稳定来实现的。以前的工作发现了一种与血清蛋白mRNAs消失相关的核酸内切酶活性，这种酶是多聚体核糖核酸酶1(PMR1)，是过氧化物酶基因家族中的一个新成员，本文研究了PMR1与其在多聚体和mRNPs上的mRNA靶标之间的关系。多聚体结合的PMR1在雌激素诱导的mRNA衰变之前被观察到最多，其在蔗糖密度梯度上的分布与多聚体结合的mRNA的吸光度曲线相匹配，这表明PMR1与mRNA形成一个潜在的复合体，在与EDTA解离后，62 kDa的PMR1与一个更大的复合体>；670 kDa沉淀。雌激素诱导多聚体结合的PMR1的单位酶活性增加22倍，并导致多聚体中PMR1的时间依赖性丢失，这反映了白蛋白mRNA的消失。这些数据表明，在雌激素诱导的广泛的非洲爪哇肝脏mRNA衰退的变化中，关键步骤是激活与其靶mRNA相关的潜伏的mRNA内切酶。
Estrogen induces a global change in the translation profile of Xenopus hepatocytes, replacing serum protein synthesis with production of the yolk protein precursor vitellogenin. This is accomplished by the coordinate destabilization of serum protein mRNAs and the transcriptional induction and subsequent stabilization of vitellogenin mRNA. Previous work identified an endonuclease activity whose appearance on polysomes correlated with the disappearance of serum protein mRNAs, This enzyme, polysomal ribonuclease 1 (PMR1), is a novel member of the peroxidase gene family, The current study examined the association of PMR1 with its mRNA targets on polysomes and mRNPs. The highest amount of polysome-bound PMR1 was observed prior to estrogen induction of mRNA decay, Its distribution on sucrose density gradients matched the absorbance profile of polysome-bound mRNA, suggesting that PMR1 forms a latent complex with mRNA, Following dissociation with EDTA the 62 kDa PMR1 sedimented with a larger complex of >670 kDa. Estrogen induces a 22-fold increase in unit enzymatic activity of polysome-bound PMR1, and a time-dependent loss of PMR1 from polysomes in a manner that mirrors the disappearance of albumin mRNA, These data suggest that the key step in the extensive estrogen-induced change in mRNA decay in Xenopus liver is activation of a latent mRNA endonuclease associated with its target mRNA.