Translational control of one-carbon metabolism underpins ribosomal protein phenotypes in cell division and longevity

Autor: Chong He, Michael Polymenis, Birgit Schilling, Heidi M. Blank, Mitsuhiro Tsuchiya, Rodolfo Aramayo, Matt Kaeberlein, Brian K. Kennedy, Nairita Maitra
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
S. cerevisiae
translation
Ribosome
Methionine
0302 clinical medicine
Loss of Function Mutation
Serine
Protein biosynthesis
RNA-Seq
Biology (General)
Cellular Senescence
media_common
General Neuroscience
Longevity
RNA-Binding Proteins
Translation (biology)
General Medicine
Chromosomes and Gene Expression
Cell biology
Phenotype
030220 oncology & carcinogenesis
Medicine
cell cycle
Cell Division
Research Article
Ribosomal Proteins
Saccharomyces cerevisiae Proteins
Rpl22
QH301-705.5
media_common.quotation_subject
Science
Saccharomyces cerevisiae
Biology
General Biochemistry
Genetics and Molecular Biology

03 medical and health sciences
ribosomal
longevity
Ribosomal protein
Gene Library
General Immunology and Microbiology
Eukaryotic Large Ribosomal Subunit
Wild type
RNA
Fungal

Genetics and Genomics
Ribosomal RNA
Carbon
030104 developmental biology
Gene Expression Regulation
Protein Biosynthesis
one-carbon
Zdroj: eLife, Vol 9 (2020)
eLife
Popis: A long-standing problem is how cells that lack one of the highly similar ribosomal proteins (RPs) often display distinct phenotypes. Yeast and other organisms live longer when they lack specific ribosomal proteins, especially of the large 60S subunit of the ribosome. However, longevity is neither associated with the generation time of RP deletion mutants nor with bulk inhibition of protein synthesis. Here, we queried actively dividing RP mutants through the cell cycle. Our data link transcriptional, translational, and metabolic changes to phenotypes associated with the loss of paralogous RPs. We uncovered translational control of transcripts encoding enzymes of methionine and serine metabolism, which are part of one-carbon (1C) pathways. Cells lacking Rpl22Ap, which are long-lived, have lower levels of metabolites associated with 1C metabolism. Loss of 1C enzymes increased the longevity of wild type cells. 1C pathways exist in all organisms and targeting the relevant enzymes could represent longevity interventions.
Databáze: OpenAIRE