Advances of NAT10 in diseases: insights from dual properties as protein and RNA acetyltransferase.

Abstract

N-acetyltransferase 10 (NAT10) is a member of the Gcn5-related N-acetyltransferase (GNAT) family and it plays a crucial role in various cellular processes, such as regulation of cell mitosis, post-DNA damage response, autophagy and apoptosis regulation, ribosome biogenesis, RNA modification, and other related pathways through its intrinsic protein acetyltransferase and RNA acetyltransferase activities. Moreover, NAT10 is closely associated with the pathogenesis of tumors, Hutchinson-Gilford progeria syndrome (HGPS), systemic lupus erythematosus, pulmonary fibrosis, depression and host-pathogen interactions. In recent years, mRNA acetylation has emerged as a prominent focus of research due to its pivotal role in regulating RNA stability and translation. NAT10 stands out as the sole identified modification enzyme responsible for RNA acetylation. There remains some ambiguity regarding the similarities and differences in NAT10's actions on protein and RNA substrates. While NAT10 involves acetylation modification in both cases, which is a crucial molecular mechanism in epigenetic regulation, there are significant disparities in the catalytic mechanisms, regulatory pathways, and biological processes involved. Therefore, this review aims to offer a comprehensive overview of NAT10 as a protein and RNA acetyltransferase, covering its basic catalytic features, biological functions, and roles in related diseases.