Decreasing mitochondrial RNA polymerase activity reverses biased inheritance of hypersuppressive mtDNA.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101239074 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7404 (Electronic) Linking ISSN: 15537390 NLM ISO Abbreviation: PLoS Genet Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, c2005-

DNA, Fungal/*genetics ; DNA, Mitochondrial/*genetics ; DNA-Directed RNA Polymerases/*genetics ; Mitochondria/*genetics ; RNA, Mitochondrial/*genetics; DNA Replication/genetics ; Genes, Fungal/genetics ; Replication Origin/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics ; Transcription, Genetic/genetics

Faithful inheritance of mitochondrial DNA (mtDNA) is crucial for cellular respiration/oxidative phosphorylation and mitochondrial membrane potential. However, how mtDNA is transmitted to progeny is not fully understood. We utilized hypersuppressive mtDNA, a class of respiratory deficient Saccharomyces cerevisiae mtDNA that is preferentially inherited over wild-type mtDNA (rho+), to uncover the factors governing mtDNA inheritance. We found that some regions of rho+ mtDNA persisted while others were lost after a specific hypersuppressive takeover indicating that hypersuppressive preferential inheritance may partially be due to active destruction of rho+ mtDNA. From a multicopy suppression screen, we found that overexpression of putative mitochondrial RNA exonuclease PET127 reduced biased inheritance of a subset of hypersuppressive genomes. This suppression required PET127 binding to the mitochondrial RNA polymerase RPO41 but not PET127 exonuclease activity. A temperature-sensitive allele of RPO41 improved rho+ mtDNA inheritance over a specific hypersuppressive mtDNA at semi-permissive temperatures revealing a previously unknown role for rho+ transcription in promoting hypersuppressive mtDNA inheritance.
Competing Interests: The authors have declared that no competing interests exist. Author Angelika Amon was unable to confirm their authorship contributions. On their behalf, the corresponding author has reported their contributions to the best of their knowledge.

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R35 GM118066 United States GM NIGMS NIH HHS

Dryad 10.5061/dryad.547d7wm8v; 10.5061/dryad.cfxpnvx5z; 10.5061/dryad.cfxpnvx5z

0 (DNA, Fungal)
0 (DNA, Mitochondrial)
0 (RNA, Mitochondrial)
0 (Saccharomyces cerevisiae Proteins)
EC 2.7.7.6 (DNA-Directed RNA Polymerases)

Date Created: 20211019 Date Completed: 20211130 Latest Revision: 20211130

20240829

PMC8555793

10.1371/journal.pgen.1009808

34665800