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The human mitochondrial genome contains a second light strand promoter

Lookup NU author(s): Dr Katja MengerORCiD, Dr Thomas NichollsORCiD, Professor Patrick Chinnery

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

The human mitochondrial genome must be replicated and expressed in a timely manner to maintain energy metabolism and supply cells with adequate levels of adenosine triphosphate. Central to this process is the idea that replication primers and gene products both arise via transcription from a single light strand promoter (LSP) such that primer formation can influence gene expression, with no consensus as to how this is regulated. Here, we report the discovery of a second light strand promoter (LSP2) in humans, with features characteristic of a bona fide mitochondrial promoter. We propose that the position of LSP2 on the mitochondrial genome allows replication and gene expression to be orchestrated from two distinct sites, which expands our long-held understanding of mitochondrial gene expression in humans.


Publication metadata

Author(s): Tan BG, Mutti CD, Shi Y, Xie X, Zhu X, Silva-Pinheiro P, Menger KE, Díaz-Maldonado H, Wei W, Nicholls TJ, Chinnery PF, Minczuk M, Falkenberg M, Gustafsson CM

Publication type: Article

Publication status: Published

Journal: Molecular Cell

Year: 2022

Volume: 82

Issue: 19

Pages: 3646-3660.e9

Print publication date: 06/10/2022

Online publication date: 30/08/2022

Acceptance date: 07/08/2022

Date deposited: 30/08/2022

ISSN (print): 1097-2765

ISSN (electronic): 1097-4164

Publisher: Cell Press

URL: https://doi.org/10.1016/j.molcel.2022.08.011

DOI: 10.1016/j.molcel.2022.08.011


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Funding

Funder referenceFunder name
213464/Z/18/ZWellcome Trust
ALFGBG-965954
2016-683191
2017-01257
2018.0204
2019-816
2020-1291
2021-00932
ALFGBG-966275
KAW 2017.0080
MC_UU_00015/4
MC_UU_00028/3

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