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Expression data from Arabidopsis thaliana depleted of HYPK or NAA10

ABSTRACT: N-alpha terminal acetylation is an abundant protein modification in eukaryotes. The NatA (N-alpha acetyltransferase A) complex is responsible for N-terminal acetylation of majority of the cytosolic proteins and its core is composed of NAA10 and NAA15 subunit. HYPK has been shown to interact with NatA core complex in human and fungus, modulating its activity. Here we address the in vivo function of the plant HYPK protein. A transcriptomics approach was applied to compare transcriptional reprogramming induced by depletion of NAA10 or HYPK mutants in plants.

ORGANISM(S): Arabidopsis thaliana

PROVIDER: GSE158586 | GEO | 2022/05/20

REPOSITORIES: GEO

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Project description:Rationale- NAA15 is a component of the N-terminal (Nt) acetyltransferase complex, NatA. The mechanism by which NAA15 haploinsufficiency causes congenital heart disease (CHD) remains unknown. To better understand molecular processes by which NAA15 haploinsufficiency perturbs cardiac development, we introduced NAA15 variants into human induced pluripotent stem cells (iPSCs) and assessed the consequences of these mutations on RNA and protein expression. Objective- We aim to understand the role of NAA15 haploinsufficiency in cardiac development by investigating proteomic effects on NatA complex activity, and identifying proteins dependent upon a full amount of NAA15.Methods and Results - We introduced heterozygous LoF, compound heterozygous and missense residues (R276W) in iPS cells using CRISPR/Cas9. Haploinsufficient NAA15 iPS cells differentiate into cardiomyocytes, unlike NAA15-null iPS cells, presumably due to altered composition of NatA. Mass spectrometry (MS) analyses reveal ~80% of identified iPS cell NatA targeted proteins displayed partial or complete Nt-acetylation. Between null and haploinsufficient NAA15 cells Nt-acetylation levels of 32 and 9 NatA-specific targeted proteins were reduced, respectively. Similar acetylation loss in few proteins occurred in NAA15 R276W iPSCs. In addition, steady-state protein levels of 562 proteins were altered in both null and haploinsufficient NAA15 cells; eighteen were ribosomal-associated proteins. At least four proteins were encoded by genes known to cause autosomal dominant CHD. Conclusions - These studies define a set of human proteins that requires a full NAA15 complement for normal synthesis and development. A 50% reduction in the amount of NAA15 alters levels of at least 562 proteins and Nt-acetylation of only 9 proteins. One or more modulated proteins are likely responsible for NAA15-haploinsufficiency mediated CHD. Additionally, genetically engineered iPS cells provide a platform for evaluating the consequences of amino acid sequence variants of unknown significance on NAA15 function.

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Expression data from Arabidopsis thaliana depleted of HYPK or NAA10

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