Translational regulation of RPA2 via internal ribosomal entry site and by eIF3a
Translational regulation of RPA2 via internal ribosomal entry site and by eIF3a
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RPA2 通过内部核糖体进入位点和 eIF3a 的翻译调节
DOI：
10.1093/carcin/bgt052
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发表时间：
2013-06-01
期刊：
影响因子：
4.7
通讯作者：
Zhang, Jian-Ting
中科院分区：
文献类型：
--
作者：
Yin, Ji-Ye;Dong, Zi-Zheng;Zhang, Jian-Ting
RPA2是三聚体复制蛋白a （RPA）复合体的一个亚基，对DNA修复和复制至关重要。虽然已知RPA活性受翻译后修饰调控，但RPA表达是否受到调控及其机制尚不清楚。eIF3a是eIF3的最大亚基，在翻译控制中起着重要作用，并被认为可以调节对肿瘤发生、转移、细胞周期进展、药物反应和DNA修复至关重要的信使rna亚群的翻译。在本研究中，我们发现RPA2的表达在翻译水平上是通过内部核糖体进入位点（IRES）介导的起始来调节的，以响应DNA损伤。我们还发现eIF3a通过直接结合位于翻译起始位点上游50 - 150个碱基的RPA2的IRES元件，抑制RPA2的合成并抑制其细胞IRES活性。综上所述，我们得出结论，RPA2的表达受IRES和eIF3a的翻译调节，这种调节在一定程度上解释了细胞对DNA损伤和存活的反应。
RPA2 is a subunit of a trimeric replication protein A (RPA) complex important for DNA repair and replication. Although it is known that RPA activity is regulated by post-translational modification, whether RPA expression is regulated and the mechanism therein is currently unknown. eIF3a, the largest subunit of eIF3, is an important player in translational control and has been suggested to regulate translation of a subset of messenger RNAs important for tumorigenesis, metastasis, cell cycle progression, drug response and DNA repair. In the present study, we show that RPA2 expression is regulated at translational level via internal ribosome entry site (IRES)-mediated initiation in response to DNA damage. We also found that eIF3a suppresses RPA2 synthesis and inhibits its cellular IRES activity by directly binding to the IRES element of RPA2 located at 50 to 150 bases upstream of the translation start site. Taken together, we conclude that RPA2 expression is translationally regulated via IRES and by eIF3a and that this regulation is partly accountable for cellular response to DNA damage and survival.