UC San Diego

Errors in tRNA aminoacylation can lead to misfolded proteins, which can form protein aggregates. Protein aggregation have been linked to many neurological diseases, thus understanding the mechanisms that can lead to the formation of protein aggregates is critical for researching degenerative illnesses. Aminoacyl tRNA synthetases (AARSs) have been found to have hydrolytic editing functions that can correct tRNA mischarging errors and prevent mistranslation. A mutation, referred to as sticky, has been discovered to cause a dysfunction in the hydrolytic editing function of alanyl-tRNA synthetase (AlaRS), resulting in mischarged Ser-tRNAAla and causes serine to be incorrectly incorporated into newly-formed peptides. However, Ankrd16, a newly discovered protein, has been found to aid AlaRS in editing of mischarged tRNAs by removing serine from the aminoacyl active site of AlaRS. By conditionally deleting Ankrd16 in CaMKIIa-positive neurons in the forebrain of Aars^sti/sti mice, the Ackerman lab was able to induce neuronal death in targeted neurons (Vo et al., 2018). In this study, we attempted to induce motor neuron death by conditionally deleting Ankrd16 in ChAT-positive motor neurons in Aars^sti/sti mice. Although motor neuron death was not observed, other phenotypes, such as decreased weight, kyphosis, and decreased axon diameters were found to be caused by the conditional deletion of Ankrd16. These results suggest that motor neurons may be more resistant to Ankrd16 loss than other neurons, such as Purkinje cells.