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Ribosomal Readthrough at a Short UGA Stop Codon Context Triggers Dual Localization of Metabolic Enzymes in Fungi and Animals


Eukaryotic organisms use various strategies to generate protein isoforms with different function or intracellular localization from a single gene. While differential splicing of mRNA is the most common mechanism to expand the number of encoded proteins, translational readthrough of stop codons is an alternative strategy to create protein variants with C-terminally extended proteins. Recently, it has been shown that fungi use both alternative splicing and translational readthrough to specify peroxisomal isoforms of glycolytic enzymes. Here we show that stop codon readthrough is also used in the animal kingdom to target important metabolic enzymes to peroxisomes. Interestingly, several of these enzymes have a function in peroxisomal redox homeostasis and energy metabolism. It has been described that termination fidelity is modulated by oxidation of specific ribosomal proteins. This suggests that dual targeting via translational readthrough allows adaptation of peroxisomal metabolism to the oxidative status of the cell.


Vyšlo v časopise: Ribosomal Readthrough at a Short UGA Stop Codon Context Triggers Dual Localization of Metabolic Enzymes in Fungi and Animals. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004685
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004685

Souhrn

Eukaryotic organisms use various strategies to generate protein isoforms with different function or intracellular localization from a single gene. While differential splicing of mRNA is the most common mechanism to expand the number of encoded proteins, translational readthrough of stop codons is an alternative strategy to create protein variants with C-terminally extended proteins. Recently, it has been shown that fungi use both alternative splicing and translational readthrough to specify peroxisomal isoforms of glycolytic enzymes. Here we show that stop codon readthrough is also used in the animal kingdom to target important metabolic enzymes to peroxisomes. Interestingly, several of these enzymes have a function in peroxisomal redox homeostasis and energy metabolism. It has been described that termination fidelity is modulated by oxidation of specific ribosomal proteins. This suggests that dual targeting via translational readthrough allows adaptation of peroxisomal metabolism to the oxidative status of the cell.


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