Naa12 compensates for Naa10 in mice in the amino-terminal acetylation pathway

Abstract

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 lacking <i>Naa10</i> show no globally apparent in vivo amino-terminal acetylation impairment and do not exhibit complete embryonic lethality. Rather <i>Naa10</i> nulls 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. <i>Naa12</i> is a previously unannotated <i>Naa10</i>-like paralog with NAT activity that genetically compensates for <i>Naa10</i>. Mice deficient for <i>Naa12</i> have no apparent phenotype, whereas mice deficient for <i>Naa10</i> and <i>Naa12</i> display embryonic lethality. The discovery of <i>Naa12</i> adds to the currently known machinery involved in amino-terminal acetylation in mice.