du Mee, Dorine Jeanne MariëtteIvanov, MaximParker, Joseph PaulBuratowski, StephenMarquardt, Sebastian2018-04-192018du Mee, Dorine Jeanne Mariëtte, Maxim Ivanov, Joseph Paul Parker, Stephen Buratowski, and Sebastian Marquardt. 2018. “Efficient termination of nuclear lncRNA transcription promotes mitochondrial genome maintenance.” eLife 7 (1): e31989. doi:10.7554/eLife.31989. http://dx.doi.org/10.7554/eLife.31989.http://nrs.harvard.edu/urn-3:HUL.InstRepos:35982201Most DNA in the genomes of higher organisms does not code for proteins. RNA Polymerase II (Pol II) transcribes non-coding DNA into long non-coding RNAs (lncRNAs), but biological roles of lncRNA are unclear. We find that mutations in the yeast lncRNA CUT60 result in poor growth. Defective termination of CUT60 transcription causes read-through transcription across the ATP16 gene promoter. Read-through transcription localizes chromatin signatures associated with Pol II elongation to the ATP16 promoter. The act of Pol II elongation across this promoter represses functional ATP16 expression by a Transcriptional Interference (TI) mechanism. Atp16p function in the mitochondrial ATP-synthase complex promotes mitochondrial DNA stability. ATP16 repression by TI through inefficient termination of CUT60 therefore triggers mitochondrial genome loss. Our results expand the functional and mechanistic implications of non-coding DNA in eukaryotes by highlighting termination of nuclear lncRNA transcription as mechanism to stabilize an organellar genome.en-USRNA Polymerase IIlncRNATranscriptional InterferenceChromatinPervasive transcriptionGenome StabilityJournal Article2018-04-1910.7554/eLife.31989