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 |
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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 |
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