N端乙酰转移酶(NAT)是在真核蛋白质上沉积大量N端乙酰化(Nt-Ac)的蛋白质复合物,目前已经确定了七个人类复合体。尽管人们越来越认识到它们的生物学和临床重要性,NAT监管仍然难以捉摸。在这项研究中,我们进行了生物信息学研究,以鉴定可能参与人类NAT复合物调控的转录和转录后过程.首先,对独立转录组数据集的共表达分析揭示了人类NAT的不同途径关联,它们可能与它们独特的细胞功能有关。发现的一个有趣的联系是癌症和免疫细胞中NatA和蛋白酶体基因的协调调节,通过对多个数据集和分离的原代T细胞的分析证实。另一个独特的关联是NAA40(NatD)与DNA复制,在癌症和非癌症环境中。NAA40转录和DNA复制之间的联系可能是通过E2F1介导的,我们已经通过实验证明E2F1结合该NAT的启动子。第二,转录组和蛋白质组数据集的耦合检查显示,与转录水平相比,蛋白质上NAT亚基的复合物内一致性更大,表明转录后过程在实现其协调方面的优势。与这个概念一致,我们还发现,影响NAT基因的体细胞拷贝数改变的影响在转录后减弱。总之,这项研究为人类NAT复合物的调控提供了新的见解。
N-terminal acetyltransferases (NAT) are the protein complexes that deposit the abundant N-terminal acetylation (Nt-Ac) on eukaryotic proteins, with seven human complexes currently identified. Despite the increasing recognition of their biological and clinical importance, NAT regulation remains elusive. In this study, we performed a bioinformatic investigation to identify transcriptional and post-transcriptional processes that could be involved in the regulation of human NAT complexes. First, co-expression analysis of independent transcriptomic datasets revealed divergent pathway associations for human NAT, which are potentially connected to their distinct cellular functions. One interesting connection uncovered was the coordinated regulation of the NatA and proteasomal genes in cancer and immune cells, confirmed by analysis of multiple datasets and in isolated primary T cells. Another distinctive association was of NAA40 (NatD) with DNA replication, in cancer and non-cancer settings. The link between NAA40 transcription and DNA replication is potentially mediated through E2F1, which we have experimentally shown to bind the promoter of this NAT. Second, the coupled examination of transcriptomic and proteomic datasets revealed a much greater intra-complex concordance of NAT subunits at the protein compared to the transcript level, indicating the predominance of post-transcriptional processes for achieving their coordination. In agreement with this concept, we also found that the effects of somatic copy number alterations affecting NAT genes are attenuated post-transcriptionally. In conclusion, this study provides novel insights into the regulation of human NAT complexes.