Biochemical Characterisation of the Short Isoform of Histone N-Terminal Acetyltransferase NAA40

Biomolecules. 2024 Sep 2;14(9):1100. doi: 10.3390/biom14091100.

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.

Keywords: NAA40; enzymatic assay; isoform; testis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • HEK293 Cells
  • Histones* / genetics
  • Histones* / metabolism
  • Humans
  • Isoenzymes / chemistry
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • N-Terminal Acetyltransferase E / genetics
  • N-Terminal Acetyltransferase E / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism

Substances

  • Histones
  • N-Terminal Acetyltransferase E
  • Isoenzymes
  • Protein Isoforms