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.
Non-coding 7S RNA inhibits transcription via mitochondrial RNA polymerase dimerization.
Xuefeng Zhu,Xie Xie,Hrishikesh Das,Benedict G. Tan,Yonghong Shi,A. Al-Behadili,Bradley Peter,Elisa Motori,Sebastian Valenzuela,Viktor Posse,C. Gustafsson,B. Martin Hällberg,M. Falkenberg
Published 2022 in Cell
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- Publication year
2022
- Venue
Cell
- Publication date
2022-05-30
- Fields of study
Biology, Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
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