ANKRD16 prevents neuron loss caused by an editing-defective tRNA synthetase.

Document Type

Article

Publication Date

5-24-2018

JAX Source

Nature 2018 May 24; 557:510-515.

Volume

557

Issue

7706

First Page

510

Last Page

515

ISSN

1476-4687

PMID

29769718

DOI

https://doi.org/10.1038/s41586-018-0137-8

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 Aars sti 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 Aars sti 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. Nature 2018 May 24; 557:510-515.

Link to Full Text

Share

COinS