Proteomic and genomic characterization of a yeast model for Ogden syndrome
Naa10 is a N-terminal acetyltransferase that, in a complex with its auxiliary subunit Naa15, co-translationally acetylates the -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 with one of the most broad substrate ranges known. Recently, we reported an X-linked disorder of infancy, Ogden syndrome, in two families harboring a c.109T>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 thereby reducing cellular fitness, possibly due to an impaired functionality of molecular chaperones, Hsp104, Hsp40 and the Hsp70 family. Microarray and RNA-seq revealed a pseudo-diploid gene expression profile in {Delta}Naa10 cells, likely 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.