Ribosomal proteins Rpl10 and Rps6 are potent regulators of yeast replicative life span.
The yeast ribosome is composed of two subunits, the large 60S subunit (LSU) and the small 40S subunit (SSU) and harbors 78 ribosomal proteins (RPs), 59 of which are encoded by duplicate genes. Recently, deletions of the LSU paralogs RPL31A and RPL6B were found to increase significantly yeast replicative life span (RLS). RPs Rpl10 and Rps6 are known translational regulators. Here, we report that heterozygosity for rpl10Delta but not for rpl25Delta, both LSU single copy RP genes, increased RLS by 24%. Deletion of the SSU RPS6B paralog, but not of the RPS6A paralog increased replicative life span robustly by 45%, while deletion of both the SSU RPS18A, and RPS18B paralogs increased RLS moderately, but significantly by 15%. Altering the gene dosage of RPL10 reduced the translating ribosome population, whereas deletion of the RPS6A, RPS6B, RPS18A, and RPS18B paralogs produced a large shift in free ribosomal subunit stoichiometry. We observed a reduction in growth rate in all deletion strains and reduced cell size in the SSU RPS6B, RPS6A, and RPS18B deletion strains. Thus, reduction of gene dosage of RP genes belonging to both the 60S and the 40S subunit affect lifespan, possibly altering the aging process by modulation of translation.
Chiocchetti
Andreas
A
Department of Cell Biology, University of Salzburg, Hellbrunnerstrasse 34, A-5020 Salzburg, Austria.
Zhou
Jia
J
Zhu
Huashun
H
Karl
Thomas
T
Haubenreisser
Olaf
O
Rinnerthaler
Mark
M
Heeren
Gino
G
Oender
Kamil
K
Bauer
Johann
J
Hintner
Helmut
H
Breitenbach
Michael
M
Breitenbach-Koller
Lore
L
D002452:Cell Count; D002455:Cell Division / Q000235:genetics; D048429:Cell Size; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D005800:Genes, Fungal / Q000235:genetics; D006579:Heterozygote; D008957:Models, Genetic; D014176:Protein Biosynthesis / Q000235:genetics; D038601:Ribosomal Protein S6 / Q000235:genetics*; D012269:Ribosomal Proteins / Q000235:genetics*; D012270:Ribosomes / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*
C093333:RPL10 protein, S cerevisiae; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins