Ribonuclease/angiogenin inhibitor 1 regulates stress-induced subcellular localization of angiogenin to control growth and survival
Ribonuclease/angiogenin inhibitor 1 regulates stress-induced subcellular localization of angiogenin to control growth and survival
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DOI：
10.1242/jcs.134551
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发表时间：
2013-09-15
影响因子：
4
通讯作者：
Hu, Guo-fu
中科院分区：
文献类型：
--
作者：
Pizzo, Elio;Sarcinelli, Carmen;Hu, Guo-fu
血管生成素（ANG）促进细胞生长和存活。在生长条件下，ANG经历核易位并在核仁中积累，刺激rRNA转录。当细胞处于应激状态时，ANG介导trna衍生的应激诱导小RNA （tiRNA）的产生，将蛋白质翻译重新编程为一种生存机制。ANG的核糖核溶解活性对这两个过程都是必不可少的，但这种活性是如何调节的尚不清楚。我们在这里报道核糖核酸酶/血管生成素抑制剂1 （RNH1）控制ANG的定位和活性。在生长条件下，ANG位于细胞核内，不与RNH1结合，因此保留了核糖解核活性，保证了rRNA转录。胞质ANG与RNH1相关并受到RNH1的抑制，从而阻止细胞RNA的随机切割。在胁迫条件下，ANG定位于细胞质，并集中在胁迫颗粒中，与RNH1无关，因此对tiRNA的产生保持酶活性。相反，在应激细胞中，核ANG与RNH1相关，以确保酶活性被抑制，并且不会产生不必要的rRNA来节省合成代谢能量。敲低RNH1可消除应激诱导的ANG再定位，降低细胞生长和存活。
Angiogenin (ANG) promotes cell growth and survival. Under growth conditions, ANG undergoes nuclear translocation and accumulates in the nucleolus where it stimulates rRNA transcription. When cells are stressed, ANG mediates the production of tRNA-derived stress-induced small RNA (tiRNA), which reprograms protein translation into a survival mechanism. The ribonucleolytic activity of ANG is essential for both processes but how this activity is regulated is unknown. We report here that ribonuclease/angiogenin inhibitor 1 (RNH1) controls both the localization and activity of ANG. Under growth conditions, ANG is located in the nucleus and is not associated with RNH1 so that the ribonucleolytic activity is retained to ensure rRNA transcription. Cytoplasmic ANG is associated with and inhibited by RNH1 so that random cleavage of cellular RNA is prevented. Under stress conditions, ANG is localized to the cytoplasm and is concentrated in stress granules where it is not associated with RNH1 and thus remains enzymatically active for tiRNA production. By contrast, nuclear ANG is associated with RNH1 in stressed cells to ensure that the enzymatic activity is inhibited and no unnecessary rRNA is produced to save anabolic energy. Knockdown of RNH1 abolished stress-induced relocalization of ANG and decreased cell growth and survival.