MAF1 is a chronic repressor of RNA polymerase III transcription in the mouse.
- Bonhoure N Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015, Lausanne, Switzerland.
- Praz V Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015, Lausanne, Switzerland.
- Moir RD Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
- Willemin G Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015, Lausanne, Switzerland.
- Mange F Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015, Lausanne, Switzerland.
- Moret C Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015, Lausanne, Switzerland.
- Willis IM Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. ian.willis@einstein.yu.edu.
- Hernandez N Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015, Lausanne, Switzerland. nouria.hernandez@unil.ch.
- 2020-07-21
Published in:
- Scientific reports. - 2020
English
Maf1-/- mice are lean, obesity-resistant and metabolically inefficient. Their increased energy expenditure is thought to be driven by a futile RNA cycle that reprograms metabolism to meet an increased demand for nucleotides stemming from the deregulation of RNA polymerase (pol) III transcription. Metabolic changes consistent with this model have been reported in both fasted and refed mice, however the impact of the fasting-refeeding-cycle on pol III function has not been examined. Here we show that changes in pol III occupancy in the liver of fasted versus refed wild-type mice are largely confined to low and intermediate occupancy genes; high occupancy genes are unchanged. However, in Maf1-/- mice, pol III occupancy of the vast majority of active loci in liver and the levels of specific precursor tRNAs in this tissue and other organs are higher than wild-type in both fasted and refed conditions. Thus, MAF1 functions as a chronic repressor of active pol III loci and can modulate transcription under different conditions. Our findings support the futile RNA cycle hypothesis, elaborate the mechanism of pol III repression by MAF1 and demonstrate a modest effect of MAF1 on global translation via reduced mRNA levels and translation efficiencies for several ribosomal proteins.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.1038/s41598-020-68665-0
- PMID 32686713
- Persistent URL
- https://sonar.ch/global/documents/24769
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