Cited by 69Mitochondrial Function and PathologyGenomics and Chromatin DynamicsRNA and protein synthesis mechanisms

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

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Zhu, Xuefeng, Xie, Xie, Das, Hrishikesh, Tan, Benedict G., Shi, Yonghong, Al-Behadili, Ali, Peter, Bradley, Motori, Elisa +5 more·2022·Cell

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.

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Authors
Zhu, X., Xie, X., Das, H., Tan, B. G., Shi, Y., Al-Behadili, A., Peter, B., Motori, E., Valenzuela, S., Posse, V., Gustafsson, C. M., Hällberg, B. M., & Falkenberg, M.
Affiliations
  • University of Gothenburg (SE)
  • Karolinska Institutet (SE)
  • University of Cologne (DE)
Corresponding author
  • Hällberg, B. Martin
  • Falkenberg, Maria
Venue
Cell
Publisher
Elsevier BV
Published
2022-06
Volume
185
Issue
13
Pages
2309-2323.e24
ISSN
0092-8674 (ISSN-L)
OpenAlex
W4281995370
Cited by
69
References
70
Citations by year
2026: 14 · 2025: 20 · 2024: 19 · 2023: 11 · 2022: 5
FWCI
4.49
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
7S RNA, mitochondrial RNA polymerase, RNA-protein interactions, transcriptional regulation, mitochondrial transcription, non-coding RNA, negative feedback loop, transcription initiation, oxidative phosphorylation
MeSH terms
RNA, Mitochondrial, Animals, DNA, Mitochondrial, Humans, Mammals, RNA, DNA-Directed RNA Polymerases, Transcription, Genetic, Signal Recognition Particle, Dimerization, RNA, Small Cytoplasmic, Mitochondrial Proteins

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