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Essential nontranslational functions of tRNA synthetases

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Abstract

Nontranslational functions of vertebrate aminoacyl tRNA synthetases (aaRSs), which catalyze the production of aminoacyl-tRNAs for protein synthesis, have recently been discovered. Although these new functions were thought to be 'moonlighting activities', many are as critical for cellular homeostasis as their activity in translation. New roles have been associated with their cytoplasmic forms as well as with nuclear and secreted extracellular forms that affect pathways for cardiovascular development and the immune response and mTOR, IFN-γ and p53 signaling. The associations of aaRSs with autoimmune disorders, cancers and neurological disorders further highlight nontranslational functions of these proteins. New architecture elaborations of the aaRSs accompany their functional expansion in higher organisms and have been associated with the nontranslational functions for several aaRSs. Although a general understanding of how these functions developed is limited, the expropriation of aaRSs for essential nontranslational functions may have been initiated by co-opting the amino acid–binding site for another purpose.

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Figure 1: The nontranslational functions of aaRSs.
Figure 2: Amino acid–binding pocket has a vital role in some of the nontranslational functions.
Figure 3: New domains that introduce and regulate nontranslational functions.
Figure 4: Multifaceted aaRSs scaffold proteins.
Figure 5: New functions of aaRS fragments.
Figure 6: Potential therapeutic interventions derived from aaRS nontranslational functions.

Change history

  • 22 February 2012

    In the version of this article initially published online, Min Guo's name was misspelled. The error has been corrected in the HTML version of the article.

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Acknowledgements

This work was supported by US National Institutes of Health (NIH) grant GM 23562 and NCI grant CA92577 and by a fellowship from the US National Foundation for Cancer Research (P.S.), by NIH grant GM 100136, a Kimmel Scholar Award for Cancer Research and by funding from the state of Florida to Scripps Florida (M.G.).

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Guo, M., Schimmel, P. Essential nontranslational functions of tRNA synthetases. Nat Chem Biol 9, 145–153 (2013). https://doi.org/10.1038/nchembio.1158

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