Non-coding 7S RNA inhibits transcription via mitochondrial RNA polymerase dimerization.

The mitochondrial genome encodes 13 components of the oxidative phosphorylation system, and altered mitochondrial transcription drives various human pathologies. A polyadenylated, non-coding RNA molecule known as 7S RNA is transcribed from a region immediately downstream of the light strand promoter in mammalian cells, and its levels change rapidly in response to physiological conditions. Here, we report that 7S RNA has a regulatory function, as it controls levels of mitochondrial transcription both in vitro and in cultured human cells. Using cryo-EM, we show that POLRMT dimerization is induced by interactions with 7S RNA. The resulting POLRMT dimer interface sequesters domains necessary for promoter recognition and unwinding, thereby preventing transcription initiation. We propose that the non-coding 7S RNA molecule is a component of a negative feedback loop that regulates mitochondrial transcription in mammalian cells. [Display omitted] • Non-coding 7S RNA regulates mitochondrial transcription in mammalian cells • 7S RNA binding induces POLRMT dimerization and prevents promoter recognition • Degradation of 7S RNA by the mtEXO complex restores POLRMT activity 7S RNA, a conserved non-coding transcript of human mitochondrial DNA, regulates mitochondrial transcription initiation by controlling mitochondrial RNA polymerase activity. [ABSTRACT FROM AUTHOR]