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

Biomolecules

Epigenetics and Gene Regulation Laboratory, Department of Biological Sciences, University of Cyprus, Nicosia 2109, Cyprus.

Published: September 2024

AI Article Synopsis

  • N-alpha-acetyltransferase 40 (NAA40) is a key enzyme involved in cancer development and resistance to chemotherapy, with a newly discovered shorter isoform showing distinct properties.
  • The shorter NAA40 isoform exhibits higher enzymatic activity and better affinity for histone substrates compared to the full-length version, indicating its potential physiological significance.
  • The study also suggests that this isoform may arise from specific genetic sequences unique to primates and testes, revealing a greater functional diversity between the two NAA40 forms than previously understood.

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 (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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11430322PMC
http://dx.doi.org/10.3390/biom14091100DOI Listing

Publication Analysis

Top Keywords

naa40
10
n-terminal acetyltransferase
8
naa40 isoform
8
alternative translation
8
biochemical characterisation
4
characterisation short
4
short isoform
4
isoform histone
4
histone n-terminal
4
acetyltransferase naa40
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!