Biochemical Characterisation of the Short Isoform of Histone N-Terminal Acetyltransferase NAA40
Year: 2024
Type: article
Abstract: 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 (NAA40S) through alternative translation, which we proceeded to further characterise. Notably, recombinant NAA40S had a greater in vitro enzymatic activity and affinity towards its histone H2A/H4 substrates compared to full-length NAA40 (NAA40L). Within cells, NAA40S was enzymatically active, based on its ability to suppress the H2A/H4S1Ph antagonistic mark in CRISPR-generated NAA40 knockout cells. Finally, we show that in addition to alternative translation, the NAA40S 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.
Source: Biomolecules
DOI: 10.3390/biom14091100
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,069
Awards: Decoding Bromodomain Chromatin Reader Protein Mechanisms in DNA repair and Replication - Implications for Cancer, G261455394, G3361828699, G37165343, G4494585126, Deciphering the molecular and biological function of histone H2A.X N-terminal acetylation, G5287479406, G586489411, Mechanisms of Endogenous DNA Damage Promotion
OpenAlex ID: W4402133284