N-alpha-acetyltransferase 40 (NAA40) is an evolutionarily conserved N-terminal acetyltransferase (NAT) linked to oncogenesis and chemoresistance. A recent study reported the generation of a second, shorter NAA40 isoform (NAA40) through alternative translation, which we proceeded to further characterise. Notably, recombinant NAA40 had a greater in vitro enzymatic activity and affinity towards its histone H2A/H4 substrates compared to full-length NAA40 (NAA40). Within cells, NAA40 was enzymatically active, based on its ability to suppress the H2A/H4S1Ph antagonistic mark in CRISPR-generated knockout cells. Finally, we show that in addition to alternative translation, the NAA40 isoform could be derived from a primate and testis-specific transcript, which may align with the "out-of-testis" origin of recently evolved genes and isoforms. To summarise, our data reveal an even greater functional divergence between the two NAA40 isoforms than had been previously recognised.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11430322 | PMC |
http://dx.doi.org/10.3390/biom14091100 | DOI Listing |
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