C57BL/6JCya-Ankrd16^em1flox/Cya

Ankrd16, encoding a vertebrate-specific protein with ankyrin repeats, plays a crucial role in maintaining translational fidelity. It binds directly to the catalytic domain of alanyl tRNA synthetase (AlaRS), acting as an amino-acid-accepting co-regulator of tRNA synthetase editing. This function is essential for preventing severe pathologies arising from defects in the editing process [1].

In Aars sti mutant mice, a mutation in the editing domain of AlaRS leads to increased production of serine-mischarged tRNAAla and cerebellar Purkinje cell degeneration. Ankrd16 acts epistatically with this Aars sti mutation. Deletion of Ankrd16 in the brains of Aarssti/sti mice causes widespread protein aggregation and neuron loss. ANKRD16 captures the serine misactivated by AlaRS via its lysine side chains, preventing serine from being charged to tRNAAla and thus precluding serine misincorporation in nascent peptides [1].

In conclusion, Ankrd16 is vital for maintaining translational accuracy by regulating AlaRS editing. Gene-knockout studies in mice have revealed its role in preventing neurodegeneration, specifically in the context of Aars-related defects. These findings contribute to understanding the mechanisms underlying neurodegenerative diseases and potentially other pathologies related to translational errors [1].