Non-coding 7S RNA inhibits transcription via mitochondrial RNA polymerase dimerization
- PMID: 35662414
- DOI: 10.1016/j.cell.2022.05.006
Non-coding 7S RNA inhibits transcription via mitochondrial RNA polymerase dimerization
Abstract
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.
Keywords: 7S RNA; POLRMT; SUV3; cryo-EM; dimer; mitochondria; mtDNA; mtEXO; non-coding RNA; transcription.
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests C.M.G. is a scientific co-founder of Pretzel Therapeutics, and M.F. is a member of its scientific advisory board.
Comment in
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ncRNA regulation of mitochondrial transcription.Nat Rev Mol Cell Biol. 2022 Aug;23(8):520. doi: 10.1038/s41580-022-00509-3. Nat Rev Mol Cell Biol. 2022. PMID: 35729218 No abstract available.
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