Naa12compensates forNaa10in mice in the amino-terminal acetylation pathway

Amino-terminal acetylation is catalyzed by a set of N-terminal acetyltransferases (NATs). The NatA complex (including X-linked Naa10 and Naa15) is the major acetyltransferase, with 40-50% of all mammalian proteins being potential substrates. However, the overall role of amino-terminal acetylation on a whole-organism level is poorly understood, particularly in mammals. Male mice lackingNaa10show no globally apparentin vivoamino-terminal acetylation impairment and do not exhibit complete embryonic lethality. RatherNaa10nulls display increased neonatal lethality, and the majority of surviving undersized mutants exhibit a combination of hydrocephaly, cardiac defects, homeotic anterior transformation, piebaldism and urogenital anomalies.Naa12is a previously unannotatedNaa10-like paralogue with NAT activity that genetically compensates forNaa10. Mice deficient forNaa12have no apparent phenotype, whereas mice deficient forNaa10andNaa12display embryonic lethality. The discovery ofNaa12adds to the currently known machinery involved in amino-terminal acetylation in mice.