Alexandrova Jana, Paulus Caroline, Rudinger-Thirion Joëlle, Jossinet Fabrice, Frugier Magali
a Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS ; IBMC ; 15 rue René Descartes; Strasbourg Cedex , France.
RNA Biol. 2015;12(12):1301-13. doi: 10.1080/15476286.2015.1086866.
The canonical activity of glycyl-tRNA synthetase (GARS) is to charge glycine onto its cognate tRNAs. However, outside translation, GARS also participates in many other functions. A single gene encodes both the cytosolic and mitochondrial forms of GARS but 2 mRNA isoforms were identified. Using immunolocalization assays, in vitro translation assays and bicistronic constructs we provide experimental evidence that one of these mRNAs tightly controls expression and localization of human GARS. An intricate regulatory domain was found in its 5'-UTR which displays a functional Internal Ribosome Entry Site and an upstream Open Reading Frame. Together, these elements hinder the synthesis of the mitochondrial GARS and target the translation of the cytosolic enzyme to ER-bound ribosomes. This finding reveals a complex picture of GARS translation and localization in mammals. In this context, we discuss how human GARS expression could influence its moonlighting activities and its involvement in diseases.
甘氨酰 - tRNA合成酶（GARS）的典型活性是将甘氨酸加载到其对应的tRNA上。然而，在翻译之外，GARS还参与许多其他功能。单个基因编码GARS的胞质和线粒体形式，但已鉴定出2种mRNA异构体。通过免疫定位分析、体外翻译分析和双顺反子构建体，我们提供了实验证据，表明这些mRNA之一严格控制人类GARS的表达和定位。在其5'-UTR中发现了一个复杂的调节结构域，该结构域具有功能性的内部核糖体进入位点和上游开放阅读框。这些元件共同阻碍了线粒体GARS的合成，并将胞质酶的翻译靶向内质网结合核糖体。这一发现揭示了哺乳动物中GARS翻译和定位的复杂情况。在此背景下，我们讨论了人类GARS表达如何影响其兼职活动及其与疾病的关系。
