The replicative lifespan‐extending deletion of SGF73 results in altered ribosomal gene expression in yeast

• Published in: Aging cell 2017-08, Vol.16 (4), p.785-796
• Main Authors: Mason, Amanda G., Garza, Renee M., McCormick, Mark A., Patel, Bhumil, Kennedy, Brian K., Pillus, Lorraine, La Spada, Albert R.
• Format: Article
• Language: English
• Subjects: Acetates; Acetylation; Ataxin; Ataxin-7 - deficiency; Ataxin-7 - genetics; Base Sequence; Binding Sites; Cell Division; Gene Deletion; Gene expression; Gene Expression Regulation, Fungal; Genetic aspects; Genetic transcription; genome‐wide occupancy; Histone Acetyltransferases - deficiency; Histone Acetyltransferases - genetics; Humans; Life span; longevity gene; Microbial Viability; Molecular Sequence Annotation; Nervous system diseases; Neurodegeneration; Original; Polyglutamine; Promoter Regions, Genetic; Promoters; Protein Binding; replicative lifespan; Ribosomal Proteins - genetics; Ribosomal Proteins - metabolism; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Sequence Homology, Amino Acid; Sgf73; Signal Transduction; Spinocerebellar ataxia; Spinocerebellar Ataxias - genetics; Spinocerebellar Ataxias - metabolism; Spinocerebellar Ataxias - pathology; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription; Trinucleotide repeat diseases; Trinucleotide repeats; Yeast
• ISSN: 1474-9718; 1474-9726
• DOI: 10.1111/acel.12611

Summary Sgf73, a core component of SAGA, is the yeast orthologue of ataxin‐7, which undergoes CAG–polyglutamine repeat expansion leading to the human neurodegenerative disease spinocerebellar ataxia type 7 (SCA7). Deletion of SGF73 dramatically extends replicative lifespan (RLS) in yeast. To further define the basis for Sgf73‐mediated RLS extension, we performed ChIP‐Seq, identified 388 unique genomic regions occupied by Sgf73, and noted enrichment in promoters of ribosomal protein (RP)‐encoding genes. Of 388 Sgf73 binding sites, 33 correspond to 5′ regions of genes implicated in RLS extension, including 20 genes encoding RPs. Furthermore, half of Sgf73‐occupied, RLS‐linked RP genes displayed significantly reduced expression in sgf73Δ mutants, and double null strains lacking SGF73 and a Sgf73‐regulated, RLS‐linked RP gene exhibited no further increase in replicative lifespan. We also found that sgf73Δ mutants display altered acetylation of Ifh1, an important regulator of RP gene transcription. These findings implicate altered ribosomal protein expression in sgf73Δ yeast RLS and highlight altered acetylation as a pathway of relevance for SCA7 neurodegeneration.