Bioinformatic Analysis Reveals the Association of Human N-Terminal Acetyltransferase Complexes with Distinct Transcriptional and Post-Transcriptional Processes.
Co-expression
N-terminal acetyltransferases
Pathways
Post-transcriptional
Protein complex
Regulation
Journal
Biochemical genetics
ISSN: 1573-4927
Titre abrégé: Biochem Genet
Pays: United States
ID NLM: 0126611
Informations de publication
Date de publication:
12 Jun 2024
12 Jun 2024
Historique:
received:
22
04
2024
accepted:
05
06
2024
medline:
12
6
2024
pubmed:
12
6
2024
entrez:
12
6
2024
Statut:
aheadofprint
Résumé
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.
Identifiants
pubmed: 38864963
doi: 10.1007/s10528-024-10860-z
pii: 10.1007/s10528-024-10860-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Research and Innovation Foundation
ID : EXCELLENCE/ 0421/0152
Organisme : Research and Innovation Foundation
ID : EXCELLENCE/ 0421/0152
Organisme : Research and Innovation Foundation
ID : EXCELLENCE/ 0421/0152
Informations de copyright
© 2024. The Author(s).
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