Tshori Sagi, Razin Ehud, Nechushtan Hovav
Department of Nuclear Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Top Curr Chem. 2014;344:189-206. doi: 10.1007/128_2013_426.
In this chapter we describe aminoacyl-tRNA synthetase (aaRS) production of dinucleotide polyphosphate in response to stimuli, their interaction with various signaling pathways, and the role of diadenosine tetraphosphate and diadenosine triphosphate as second messengers. The primary role of aaRS is to mediate aminoacylation of cognate tRNAs, thereby providing a central role for the decoding of genetic code during protein translation. However, recent studies suggest that during evolution, "moonlighting" or non-canonical roles were acquired through incorporation of additional domains, leading to regulation by aaRSs of a spectrum of important biological processes, including cell cycle control, tissue differentiation, cellular chemotaxis, and inflammation. In addition to aminoacylation of tRNA, most aaRSs can also produce dinucleotide polyphosphates in a variety of physiological conditions. The dinucleotide polyphosphates produced by aaRS are biologically active both extra- and intra-cellularly, and seem to function as important signaling molecules. Recent findings established the role of dinucleotide polyphosphates as second messengers.
在本章中，我们描述了氨酰-tRNA合成酶（aaRS）响应刺激产生二核苷酸多磷酸、它们与各种信号通路的相互作用，以及四磷酸二腺苷和三磷酸二腺苷作为第二信使的作用。aaRS的主要作用是介导同源tRNA的氨酰化，从而在蛋白质翻译过程中为遗传密码的解码发挥核心作用。然而，最近的研究表明，在进化过程中，通过纳入额外的结构域获得了“兼职”或非经典作用，导致aaRS对一系列重要生物过程进行调控，包括细胞周期控制、组织分化、细胞趋化性和炎症。除了tRNA的氨酰化，大多数aaRS在多种生理条件下也能产生二核苷酸多磷酸。aaRS产生的二核苷酸多磷酸在细胞外和细胞内均具有生物活性，似乎作为重要的信号分子发挥作用。最近的研究结果确立了二核苷酸多磷酸作为第二信使的作用。
