Zhu, Xuefeng, Xie, Xie, Das, Hrishikesh, Tan, Benedict G., Shi, Yonghong, Al-Behadili, Ali, Peter, Bradley, Motori, Elisa ORCID: 0000-0001-5997-6866, Valenzuela, Sebastian, Posse, Viktor, Gustafsson, Claes M., Haellberg, B. Martin and Falkenberg, Maria (2022). Non-coding 7S RNA inhibits transcription via mitochondrial RNA polymerase dimerization. Cell, 185 (13). S. 2309 - 2349. CAMBRIDGE: CELL PRESS. ISSN 1097-4172

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Zhu, XuefengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xie, XieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Das, HrishikeshUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tan, Benedict G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shi, YonghongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Al-Behadili, AliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peter, BradleyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Motori, ElisaUNSPECIFIEDorcid.org/0000-0001-5997-6866UNSPECIFIED
Valenzuela, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Posse, ViktorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gustafsson, Claes M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haellberg, B. MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Falkenberg, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-675362
DOI: 10.1016/j.cell.2022.05.006
Journal or Publication Title: Cell
Volume: 185
Number: 13
Page Range: S. 2309 - 2349
Date: 2022
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4172
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DOUBLE-STRANDED-RNA; DNA-REPLICATION; CRYO-EM; POLYNUCLEOTIDE PHOSPHORYLASE; STRUCTURAL BASIS; B2 RNA; 6S RNA; IDENTIFICATION; EXPRESSION; INITIATIONMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/67536

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