7pzp Citations

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.

Reviews citing this publication (6)

  1. Mechanisms and regulation of human mitochondrial transcription. Tan BG, Gustafsson CM, Falkenberg M. Nat Rev Mol Cell Biol 25 119-132 (2024)
  2. Mitochondrial nucleic acids in innate immunity and beyond. Yoon J, Kim S, Lee M, Kim Y. Exp Mol Med 55 2508-2518 (2023)
  3. Central dogma rates in human mitochondria. McShane E, Churchman LS. Hum Mol Genet 33 R34-R41 (2024)
  4. Human mtDNA-Encoded Long ncRNAs: Knotty Molecules and Complex Functions. Bruni F. Int J Mol Sci 25 1502 (2024)
  5. SUV3 Helicase and Mitochondrial Homeostasis. Chen PL. Int J Mol Sci 24 9233 (2023)
  6. Spatiotemporal Distribution and Function of Mitochondria in Oocytes. Kang X, Yan L, Wang J. Reprod Sci 31 332-340 (2024)

Articles citing this publication (2)

  1. ANGEL2 phosphatase activity is required for non-canonical mitochondrial RNA processing. Clemente P, Calvo-Garrido J, Pearce SF, Schober FA, Shigematsu M, Siira SJ, Laine I, Spåhr H, Steinmetzger C, Petzold K, Kirino Y, Wibom R, Rackham O, Filipovska A, Rorbach J, Freyer C, Wredenberg A. Nat Commun 13 5750 (2022)
  2. Light-strand bias and enriched zones of embedded ribonucleotides are associated with DNA replication and transcription in the human-mitochondrial genome. Xu P, Yang T, Kundnani DL, Sun M, Marsili S, Gombolay AL, Jeon Y, Newnam G, Balachander S, Bazzani V, Baccarani U, Park VS, Tao S, Lori A, Schinazi RF, Kim B, Pursell ZF, Tell G, Vascotto C, Storici F. Nucleic Acids Res 52 1207-1225 (2024)