title: The control of translational accuracy is a determinant of healthy ageing in yeast.
abstract: Life requires the maintenance of molecular function in the face of stochastic processes that tend to adversely affect macromolecular integrity. This is particularly relevant during ageing, as many cellular functions decline with age, including growth, mitochondrial function and energy metabolism. Protein synthesis must deliver functional proteins at all times, implying that the effects of protein synthesis errors like amino acid misincorporation and stop-codon read-through must be minimized during ageing. Here we show that loss of translational accuracy accelerates the loss of viability in stationary phase yeast. Since reduced translational accuracy also reduces the folding competence of at least some proteins, we hypothesize that negative interactions between translational errors and age-related protein damage together overwhelm the cellular chaperone network. We further show that multiple cellular signalling networks control basal error rates in yeast cells, including a ROS signal controlled by mitochondrial activity, and the Ras pathway. Together, our findings indicate that signalling pathways regulating growth, protein homeostasis and energy metabolism may jointly safeguard accurate protein synthesis during healthy ageing.
authors.affiliation: Kent Fungal Group, School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK t.von-der-haar@kent.ac.uk.
authors.forename: Tobias
authors.identifier: 0000-0002-6031-9254
authors.initials: T
authors.lastname: von der Haar
authors.affiliation: Kent Fungal Group, School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Leadsham
authors.affiliation: Kent Fungal Group, School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
authors.forename: Aimie
authors.initials: A
authors.lastname: Sauvadet
authors.affiliation: Kent Fungal Group, School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tarrant
authors.affiliation: Kent Fungal Group, School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
authors.forename: Ilectra S
authors.initials: IS
authors.lastname: Adam
authors.affiliation: Kent Fungal Group, School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
authors.forename: Kofo
authors.initials: K
authors.lastname: Saromi
authors.affiliation: Department of Cell Biology, University of Salzburg, Hellbrunnerstrasser 34, 5020 Salzburg, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Laun
authors.affiliation: Department of Cell Biology, University of Salzburg, Hellbrunnerstrasser 34, 5020 Salzburg, Austria.
authors.forename: Mark
authors.initials: M
authors.lastname: Rinnerthaler
authors.affiliation: Department of Cell Biology, University of Salzburg, Hellbrunnerstrasser 34, 5020 Salzburg, Austria.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Breitenbach-Koller
authors.affiliation: Department of Cell Biology, University of Salzburg, Hellbrunnerstrasser 34, 5020 Salzburg, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Breitenbach
authors.affiliation: Kent Fungal Group, School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
authors.forename: Mick F
authors.initials: MF
authors.lastname: Tuite
authors.affiliation: Kent Fungal Group, School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK c.w.gourlay@kent.ac.uk.
authors.forename: Campbell W
authors.initials: CW
authors.lastname: Gourlay
mesh_terms: D002470:Cell Survival; D016922:Cellular Senescence; D004734:Energy Metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D014176:Protein Biosynthesis; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000254:growth & development* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins
keywords: ageing; chaperones; homeostasis; protein synthesis; translational accuracy