Efficient termination of nuclear lncRNA transcription promotes mitochondrial genome maintenance.

Abstract

Most 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 <i>CUT60</i> result in poor growth. Defective termination of <i>CUT60</i> transcription causes read-through transcription across the <i>ATP16</i> gene promoter. Read-through transcription localizes chromatin signatures associated with Pol II elongation to the <i>ATP16</i> promoter. The act of Pol II elongation across this promoter represses functional <i>ATP16</i> expression by a Transcriptional Interference (TI) mechanism. Atp16p function in the mitochondrial ATP-synthase complex promotes mitochondrial DNA stability. <i>ATP16</i> repression by TI through inefficient termination of <i>CUT60</i> 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.