短型组蛋白 N-端乙酰转移酶 NAA40 的生化特性分析

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

机构信息

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

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.

出版信息

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

DOI:10.3390/biom14091100

PMID:39334865

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11430322/

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.

摘要

N-α-乙酰基转移酶 40（NAA40）是一种进化上保守的 N 端乙酰基转移酶（NAT），与致癌和化疗耐药有关。最近的一项研究报告称，通过选择性翻译产生了第二种较短的 NAA40 同工型（NAA40），我们随后对其进行了进一步的表征。值得注意的是，与全长 NAA40（NAA40）相比，重组 NAA40 在体外具有更高的酶活性和对其组蛋白 H2A/H4 底物的亲和力。在细胞内，NAA40 具有酶活性，这是基于其在 CRISPR 生成的敲除细胞中抑制 H2A/H4S1Ph 拮抗标记的能力。最后，我们表明，除了选择性翻译外，NAA40 同工型还可以源自灵长类动物和睾丸特异性转录本，这可能与最近进化基因和同工型的“睾丸外”起源相一致。总之，我们的数据揭示了两种 NAA40 同工型之间的功能差异比以前认识到的更大。