Puf3p induces translational repression of genes linked to oxidative stress
| Autor: | Paul F. G. Sims, Graham D. Pavitt, Mark P. Ashe, William Rowe, Lydia M. Castelli, Joseph L. Costello, Chris M. Grant, Christopher J. Kershaw, Simon J. Hubbard |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Saccharomyces cerevisiae Mitochondrion Biology medicine.disease_cause Ribosome Polysome Gene Expression Regulation Fungal Genetics Protein biosynthesis medicine RNA Messenger Psychological repression Regulation of gene expression RNA-Binding Proteins Translation (biology) Genomics Glutathione Cell biology Oxidative Stress Biochemistry Polyribosomes Protein Biosynthesis Oxidation-Reduction Oxidative stress Gene Deletion |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | In response to stress, the translation of many mRNAs in yeast can change in a fashion discordant with the general repression of translation. Here, we use machine learning to mine the properties of these mRNAs to determine specific translation control signals. We find a strong association between transcripts acutely translationally repressed under oxidative stress and those associated with the RNA-binding protein Puf3p, a known regulator of cellular mRNAs encoding proteins targeted to mitochondria. Under oxidative stress, a PUF3 deleted strain exhibits more robust growth than wild-type cells and the shift in translation from polysomes to monosomes is attenuated, suggesting puf3Δ cells perceive less stress. In agreement, the ratio of reduced:oxidized glutathione, a major antioxidant and indicator of cellular redox state, is increased in unstressed puf3Δ cells but remains lower under stress. In untreated conditions, Puf3p migrates with polysomes rather than ribosome-free fractions, but this is lost under stress. Finally, reverse transcriptase-polymerase chain reaction (RT-PCR) of Puf3p targets following affinity purification shows Puf3p-mRNA associations are maintained or increased under oxidative stress. Collectively, these results point to Puf3p acting as a translational repressor in a manner exceeding the global translational response, possibly by temporarily limiting synthesis of new mitochondrial proteins as cells adapt to the stress. |
| Databáze: | OpenAIRE |
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