Proteomic and genomic characterization of a yeast model for Ogden syndrome.
Naa10 is an Nα-terminal acetyltransferase that, in a complex with its auxiliary subunit Naa15, co-translationally acetylates the α-amino group of newly synthetized proteins as they emerge from the ribosome. Roughly 40-50% of the human proteome is acetylated by Naa10, rendering this an enzyme one of the most broad substrate ranges known. Recently, we reported an X-linked disorder of infancy, Ogden syndrome, in two families harbouring a c.109 T > C (p.Ser37Pro) variant in NAA10. In the present study we performed in-depth characterization of a yeast model of Ogden syndrome. Stress tests and proteomic analyses suggest that the S37P mutation disrupts Naa10 function and reduces cellular fitness during heat shock, possibly owing to dysregulation of chaperone expression and accumulation. Microarray and RNA-seq revealed a pseudo-diploid gene expression profile in ΔNaa10 cells, probably responsible for a mating defect. In conclusion, the data presented here further support the disruptive nature of the S37P/Ogden mutation and identify affected cellular processes potentially contributing to the severe phenotype seen in Ogden syndrome. Data are available via GEO under identifier GSE86482 or with ProteomeXchange under identifier PXD004923. © 2016 The Authors. Yeast published by John Wiley & Sons, Ltd.
Stanley Institute for Cognitive Genomics, One Bungtown Road, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
Max J
MJ
Dörfel
Stanley Institute for Cognitive Genomics, One Bungtown Road, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
Han
H
Fang
Stanley Institute for Cognitive Genomics, One Bungtown Road, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
Jonathan
J
Crain
Stanley Institute for Cognitive Genomics, One Bungtown Road, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
Michael
M
Klingener
Stanley Institute for Cognitive Genomics, One Bungtown Road, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
Jake
J
Weiser
Stanley Institute for Cognitive Genomics, One Bungtown Road, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
Gholson J
0000-0002-5869-0716
GJ
Lyon
D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D023281:Genomics; D006801:Humans; D013058:Mass Spectrometry; D008954:Models, Biological; D063209:N-Terminal Acetyltransferase A / Q000235:genetics / Q000502:physiology; D063213:N-Terminal Acetyltransferase E / Q000235:genetics / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D040901:Proteomics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology; D016415:Sequence Alignment; D013577:Syndrome
D063209:N-Terminal Acetyltransferase A; C504824:NAA10 protein, human; D063213:N-Terminal Acetyltransferase E
N-terminal acetyltransferase; Naa10; NatA; Ogden syndrome
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