Suppression of Biased mtDNA Inheritance by Overexpression of a RNA Nuclease
Daniel Corbi1 and Angelika Amon1* 1Massachusetts Institute of Technology *Corresponding Author
Hypersuppressive yeast mitochondrial DNA (mtDNA) is non-functional for respiration but inherited preferentially to progeny when competed with wild-type mitochondrial DNA. Hypersuppressive mitochondrial DNAs consist solely of tandem repeats of specific less than 2kb regions of wild-type mtDNA. These regions are called Oris and were thought to be origins of replication of mtDNA but create an approximately 200bp non-coding RNA of unknown function. We screened for high-copy suppressors of this preferential inheritance phenotype and found PET127, a gene encoding a putative 5'-riboexonuclease. Overexpression of Pet127, in both wild-type and cells containing hypersuppressive mtDNA, causes transcriptional upregulation of Ori RNA. This Ori RNA upregulation correlates with a downregulation of all other mitochondrial RNAs. Pet127 co-immunoprecipitates with the mitochondrial RNA polymerase, Rpo41, and, upon overexpression, reduces occupancy of Rpo41 at non-Ori mitochondrial loci. We are currently testing the hypothesis that Ori RNA transcription, caused by high levels of PET127, negatively regulates mtDNA inheritance.
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