Nα-terminal acetylation of proteins by NatA and NatB serves distinct physiological roles in Saccharomyces cerevisiae

Abstract

Highlights d Nt acetyltransferases NatA and NatB have distinct roles in cellular processes d NatA is implicated in the maintenance of chromosomal integrity d NatB plays a more important role in cellular proteostasis than NatA

Up-regulation of ubiquitin–proteasome activity upon loss of NatA-dependent N-terminal acetylation

“…We observed significantly lower protein levels in the naa10Δ mutant ( Fig S1A ), which may not be explained by the observed very weak stability differences. Friedrich et al (2021) reported altered expression/transcription levels in the absence of NatA, which could explain the differences in protein abundance. To investigate this we used qPCR to quantify tFT-mRNA and detected a ∼40% reduction of the mRNA levels of the reporter in the absence of NatA ( Fig S1B ).…”

“…Beside the changed degradation rates of UFD-substrates we also observed changed protein abundance in NatA mutants, which were potentially linked to altered mRNA levels (Fig S1A and B). Changed protein synthesis and transcription rates were already reported for NatA mutants and underline the vast cellular changes that are happening in these deletion strains (Friedrich et al, 2021). In some instances, these phenotypes made it difficult to review stability changes in cycloheximide chase experiments when protein levels were very variable between different genetic backgrounds.…”

“…For NatA, several individual targets are known where Nt-acetylation functions in mediating protein–protein interactions, prevention of incorrect protein secretion, protein folding, and degradation. This includes key transcriptional regulators as well as protein folding machinery or structural components of the cytoskeleton ( Aksnes et al, 2016 ; Friedrich et al, 2021 ); therefore, it is not surprising that the attribution of specific functions to Nα-acetylated N-termini is not possible. Another important point is the question to what extent Nt-acetylation is subject to specific regulation, for example, via regulation of the activity of the individual NATs.…”

“…Nt-acetylation was proposed to act as a degradation signal ( Hwang et al, 2010b ; Shemorry et al, 2013 ) and Nt-acetylated N-termini are thought to be recognized and ubiquitinated by specific E3 ligases of the Ac/N-end rule pathway. The universality of this pathway is debatable because acetylation is not a self-sufficient degron and the involved E3 ligases recognize a broad palette of N-degrons independent on Nt-acetylation ( Zattas et al, 2013 ; Gawron et al, 2016 ; Kats et al, 2018 ; Friedrich et al, 2021 ). Still, Nt-acetylation can be part of N-degrons that contain adjacent sequence motifs ( Hwang et al, 2010b ; Shemorry et al, 2013 ).…”

Universality and non-universality of the growth law

“…The actual shape of the growth law curve depends degradation rates (I φ,α ). By analyzing the dataset from [14], we found that I φ,α is independent of growth rate, while I χ,k appears to be negatively correlated with the growth rate. This means that cells tend to produce proteins with faster translation speeds in slow-growth conditions, which can be an economic strategy and under evolutionary selection.…”