期刊
CELL
卷 185, 期 13, 页码 2309-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2022.05.006
关键词
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资金
- National Microscopy Infrastructure, NMI [VR-RFI 2016-00968]
- Swedish Research Council [2018-03808, 2021-00932, 2017-01257]
- Swedish Cancer Foundation [2019-816, 2020-1291]
- Knut and Alice Wallenberg Foundation [KAW 2018.0080, KAW 2017.0080]
- European Research Council [2016-683191]
- Swedish Government
- Swedish county councils
- ALF agreement [ALFGBG-965954, ALFGBG-966275]
- Swedish Research Council [2017-01257, 2021-00932, 2018-03808] Funding Source: Swedish Research Council
The non-coding RNA molecule 7S RNA regulates mitochondrial transcription in mammalian cells by inducing POLRMT dimerization, which prevents transcription initiation.
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.
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