@article{5d7eba5dd3a843918ea146a9d56c655a,
title = "ANKRD16 prevents neuron loss caused by an editing-defective tRNA synthetase",
abstract = "Editing domains of aminoacyl tRNA synthetases correct tRNA charging errors to maintain translational fidelity. A mutation in the editing domain of alanyl tRNA synthetase (AlaRS) in Aarssti mutant mice results in an increase in the production of serine-mischarged tRNAAla and the degeneration of cerebellar Purkinje cells. Here, using positional cloning, we identified Ankrd16, a gene that acts epistatically with the Aarssti mutation to attenuate neurodegeneration. ANKRD16, a vertebrate-specific protein that contains ankyrin repeats, binds directly to the catalytic domain of AlaRS. Serine that is misactivated by AlaRS is captured by the lysine side chains of ANKRD16, which prevents the charging of serine adenylates to tRNAAla and precludes serine misincorporation in nascent peptides. The deletion of Ankrd16 in the brains of Aarssti/sti mice causes widespread protein aggregation and neuron loss. These results identify an amino-acid-accepting co-regulator of tRNA synthetase editing as a new layer of the machinery that is essential to the prevention of severe pathologies that arise from defects in editing.",
author = "Vo, {My Nuong} and Markus Terrey and Lee, {Jeong Woong} and Bappaditya Roy and Moresco, {James J.} and Litao Sun and Hongjun Fu and Qi Liu and Weber, {Thomas G.} and Yates, {John R.} and Kurt Fredrick and Paul Schimmel and Ackerman, {Susan L.}",
note = "Funding Information: We thank K. Brown, J. Cook, T. Jucius and A. Kano for technical assistance, and the microinjection core at The Jackson Laboratory for transgenic mouse production. This work was supported by National Institutes of Health grants R01NS42613 to S.L.A., R01GM072528 to K.F., R01CA92577 to P.S., and a Fellowship from the National Foundation for Cancer Research to P.S. S.L.A. is an investigator of the Howard Hughes Medical Institute. Funding Information: Acknowledgements We thank K. Brown, J. Cook, T. Jucius and A. Kano for technical assistance, and the microinjection core at The Jackson Laboratory for transgenic mouse production. This work was supported by National Institutes of Health grants R01NS42613 to S.L.A., R01GM072528 to K.F., R01CA92577 to P.S., and a Fellowship from the National Foundation for Cancer Research to P.S. S.L.A. is an investigator of the Howard Hughes Medical Institute. Publisher Copyright: {\textcopyright} 2018 Macmillan Publishers Ltd., part of Springer Nature.",
year = "2018",
month = may,
day = "24",
doi = "10.1038/s41586-018-0137-8",
language = "English (US)",
volume = "557",
pages = "510--515",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7706",
}