Neo-functionalization in : a Novel Nrg1-Rtg3 Chimeric Transcriptional Modulator is Essential to Maintain Mitochondrial DNA Integrity
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In the transcriptional repressor Nrg1 (Negative Regulator of Glucose-repressed genes) and the β-Zip transcription factor Rtg3 (ReTroGrade regulation) mediate glucose repression and signalling from the mitochondria to the nucleus, respectively. Here, we show a novel function of these two proteins, in which alanine promotes the formation of a chimeric Nrg1/Rtg3 regulator that represses the gene (encoding an alanine transaminase paralog of unknown function). An paralogous pair, resulting from a post-wide genome small-scale duplication event, is present in the genus. Neo-functionalization of only one paralog resulted in the ability of Nrg1 to interact with Rtg3. Both Δ and Δ single mutant strains were unable to use ethanol and showed a typical petite (small) phenotype on glucose. Neither of the wild-type genes complemented the petite phenotype, suggesting irreversible mitochondrial DNA damage in these mutants. Neither Δ nor Δ mutant strains expressed genes encoded by any of the five polycistronic units transcribed from mitochondrial DNA in . This, and the direct measurement of the mitochondrial DNA gene complement, confirmed that irreversible damage of the mitochondrial DNA occurred in both mutant strains, which is consistent with the essential role of the chimeric Nrg1/Rtg3 regulator in mitochondrial DNA maintenance.
Campero-Basaldua C, Gonzalez J, Garcia J, Ramirez E, Hernandez H, Aguirre B R Soc Open Sci. 2023; 10(11):231209.
PMID: 37920568 PMC: 10618058. DOI: 10.1098/rsos.231209.