MAF1 is a chronic repressor of RNA polymerase III transcription in the mouse.

Scientific Reports
Nicolas BonhoureNouria Hernandez

Abstract

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 ef...Continue Reading

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Citations

Dec 17, 2020·MBio·Jessica M TuckerBritt A Glaunsinger
Feb 27, 2021·Frontiers in Cellular Neuroscience·Stefanie PerrierGeneviève Bernard
Jul 24, 2021·Frontiers in Genetics·Yavuz KulaberogluJennifer M A Tullet

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Methods Mentioned

BETA
immunoprecipitation
ChIP-seq
RNA-seq
ChIPs
PCR
ChIP
electrophoresis
Ribo-seq

Software Mentioned

GSEA
cutadapt
RSeQC
isoacceptor
count
Odyssey Imaging System ( )
htseq
isotype
FastQ Screen
house

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