Termination of nuclear lncRNA transcription promotes mitochondrial genome maintenance

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. Researchers at the University of Copenhagen found 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. These 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.

The divergent non-coding transcript CUT60 promotes growth
and mitochondrial genome maintenance

(A) Schematic representation of the bidirectional promoter of MED2. CUT60 is a divergent lncRNA transcript originating from the MED2 promoter, and it is located upstream in tandem of ATP16. (B) Serial dilution growth assay of wild type and cut60Δ::URA3 strains on SC-Glucose medium (n = 3). (C) Serial dilution growth assay of wild type and cut60Δ::URA3 strains on SC-Glycerol medium (n = 3). (D) Growth of wild type, cut60Δ::URA3 and mip1Δ on SC-Glucose and SC-Glycerol after mating with cut60Δ::URA3 strain (n = 3). (E) Northern blot analysis of COX3 and SCR1 (as loading control) transcripts in mip1Δ, wild type and cut60Δ::URA3 (n = 3).

du Mee DJM, Ivanov M, Parker JP, Buratowski S, Marquardt S. (2018) Efficient termination of nuclear lncRNA transcription promotes mitochondrial genome maintenance. Elife e31989. [article]

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