Proteomic and genomic characterization of a yeast model for Ogden syndrome

Dorfel, M. J., Fang, H., Crain, J., Klingener, M., Weiser, J., Lyon, G. J. (2017) Proteomic and genomic characterization of a yeast model for Ogden syndrome. Yeast, 34 (1). pp. 19-37. ISSN 1097-0061 (Electronic)0749-503X (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/27668839
DOI: 10.1002/yea.3211

Abstract

Naa10 is a Nalpha -terminal acetyltransferase that, in a complex with its auxiliary subunit Naa15, co-translationally acetylates the alpha-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.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 due to dysregulation of chaperone expression and accumulation. Microarray and RNA-seq revealed a pseudo-diploid gene expression profile in DeltaNaa10 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. Data are available via GEO under identifier GSE86482 or with ProteomeXchange under identifier PXD004923.

Item Type: Paper
Subjects: diseases & disorders > congenital hereditary genetic diseases
bioinformatics > genomics and proteomics
diseases & disorders > congenital hereditary genetic diseases > mental retardation
organism description > yeast
CSHL Authors:
Communities: CSHL labs > Lyon lab
Depositing User: Matt Covey
Date Deposited: 28 Sep 2016 20:07
Last Modified: 24 Mar 2017 16:14
PMCID: PMC5248646
Related URLs:
URI: http://repository.cshl.edu/id/eprint/33549

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