Identification of an alternatively spliced nuclear isoform of human N-terminal acetyltransferase Naa30

Abstract N-terminal acetylation is a highly abundant and important protein modification in eukaryotes catalyzed by N-terminal acetyltransferases (NATs). In humans, six different NATs have been identified (NatA-NatF), each composed of individual subunits and acetylating a distinct set of substrates. Along with most NATs, NatC acts co-translationally at the ribosome. The NatC complex consists of the catalytic subunit Naa30 and the auxiliary subunits Naa35 and Naa38, and can potentially Nt-acetylate cytoplasmic proteins when the initiator methionine is followed by a bulky hydrophobic/amphipathic residue at position 2. Here, we have identified a splice variant of human NAA30 , which encodes a truncated protein named Naa30 288 . The splice variant was abundantly present in thyroid cancer tissues and in several different human cancer cell lines. Surprisingly, Naa30 288 localized predominantly to the nucleus, as opposed to annotated Naa30 which has a cytoplasmic localization. Full-length Naa30 acetylated a classical NatC substrate peptide in vitro , whereas no significant NAT activity was detected for Naa30 288. Due to the nuclear localization, we also examined acetyltransferase activity towards lysine residues. Neither full-length Naa30 nor Naa30 288 displayed any lysine acetyltransferase activity. Overexpression of full-length Naa30 increased cell viability via inhibition of apoptosis. In contrast, Naa30 288 did not exert an anti-apoptotic effect. In sum, we identified a novel and widely expressed Naa30 isoform with a potential non-catalytic role in the nucleus.