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Series GSE83368 Query DataSets for GSE83368
Status Public on Aug 05, 2016
Title POLRMT regulates the switch between replication-primer formation and gene expression of mammalian mtDNA
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Mitochondria are vital in providing cellular energy via their oxidative phosphorylation system, which requires the coordinated expression of genes encoded by both the nuclear and mitochondrial genomes (mtDNA). Transcription of the circular mammalian mtDNA depends on a single mitochondrial RNA polymerase (POLRMT). Although the transcription initiation process is well understood, it remains highly controversial if POLRMT also serves as the primase for initiation of mtDNA replication. In the nucleus, the RNA polymerases needed for gene expression have no such role. Conditional knockout of Polrmt in heart results in severe mitochondrial dysfunction causing dilated cardiomyopathy in young mice. We further studied the molecular consequences of different expression levels of POLRMT and found that POLRMT is essential for primer synthesis to initiate mtDNA replication in vivo. Furthermore, transcription initiation for primer formation has priority over gene expression. Surprisingly, mitochondrial transcription factor A (TFAM) exists in an mtDNA-free pool in the Polrmt knockout mice. TFAM levels remain unchanged despite strong mtDNA depletion and TFAM is thus protected from degradation of the AAA+ Lon protease in absence of POLRMT. Lastly, mitochondrial transcription elongation factor (TEFM) can compensate for a partial depletion of POLRMT in heterozygous Polrmt knockout mice, indicating a direct regulatory role for this factor in transcription. In conclusion, we present here the first in vivo evidence that POLRMT has a key regulatory role in replication of mammalian mtDNA and is part of a mechanism that provides a switch between RNA primer formation for mtDNA replication and mtDNA expression.
 
Overall design Isolated heart mitochondria from three control mice (L/L) and three Polrmt knockout mice (L/L, cre), aged 3-4 weeks, were sequenced and analyzed for differential expression.
 
Contributor(s) Siira SJ, Filipovska A
Citation(s) 27532055
Submission date Jun 15, 2016
Last update date May 15, 2019
Contact name Stefan J Siira
Organization name Harry Perkins Institute of Medical Research
Department Molecular medicine
Lab Mitochondrial medicine and biology
Street address 6 Verdun St, Nedlands
City Perth
State/province Western Australia
ZIP/Postal code 6009
Country Australia
 
Platforms (1)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (6)
GSM2200349 L/L, rep1
GSM2200350 L/L, rep2
GSM2200351 L/L, rep3
Relations
BioProject PRJNA325725
SRA SRP076586

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Supplementary file Size Download File type/resource
GSE83368_RAW.tar 870.0 Kb (http)(custom) TAR (of TXT)
GSE83368_edgeR_results.txt.gz 258.3 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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