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TitleNon-coding 7S RNA inhibits transcription via mitochondrial RNA polymerase dimerization.
Journal, issue, pagesCell, Vol. 185, Issue 13, Page 2309-2323.e24, Year 2022
Publish dateJun 23, 2022
AuthorsXuefeng Zhu / Xie Xie / Hrishikesh Das / Benedict G Tan / Yonghong Shi / Ali Al-Behadili / Bradley Peter / Elisa Motori / Sebastian Valenzuela / Viktor Posse / Claes M Gustafsson / B Martin Hällberg / Maria Falkenberg /
PubMed AbstractThe mitochondrial genome encodes 13 components of the oxidative phosphorylation system, and altered mitochondrial transcription drives various human pathologies. A polyadenylated, non-coding RNA ...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.
External linksCell / PubMed:35662414
MethodsEM (single particle)
Resolution3.0 - 3.5 Å
Structure data

13735

7pzp

EMDB-13735, PDB-7pzp:
Mitochondrial DNA dependent RNA polymerase homodimer.
Method: EM (single particle) / Resolution: 3.5 Å

13736

7pzr

EMDB-13736, PDB-7pzr:
Cryo-EM structure of POLRMT in free form.
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-13796: 2021-10-18
Method: EM (single particle) / Resolution: 3.5 Å

14619

7zc4

EMDB-14619, PDB-7zc4:
Cryo-EM structure of POLRMT mutant.
Method: EM (single particle) / Resolution: 3.24 Å

Source
  • homo sapiens (human)
KeywordsTRANSCRIPTION / Mitochondria / DNA dependent RNA polymerase / 7S RNA / DNA dependent RNA polymerase.

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