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Lookup NU author(s): Dr Thomas NichollsORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
Oligoribonucleases are conserved enzymes that degrade short RNA molecules of up to 5 nt in length, and are assumed to constitute the final stage of RNA turnover. We here demonstrate that REXO2 is a specialised dinucleotide degrading enzyme that shows no preference between RNA and DNA dinucleotide substrates. A heart and skeletal muscle-specific knockout mouse displays elevated dinucleotide levels and alterations in gene expression patterns indicative of aberrant dinucleotide-primed transcription initiation. We find that dinucleotides act as potent stimulators of mitochondrial transcription initiation in vitro. Our data demonstrate that increased levels of dinucleotides can be used to initiate transcription, leading to an increase in transcription levels from both mitochondrial promoters and other, nonspecific sequence elements in mitochondrial DNA. Efficient RNA turnover by REXO2 is thus required to maintain promoter specificity and proper regulation of transcription in mammalian mitochondria.
Author(s): Nicholls TJ, Spåhr H, Jiang S, Siira SJ, Koolmeister C, Sharma S, Kauppila JHK, Jiang M, Kaever V, Rackham O, Chabes A, Falkenberg M, Filipovska A, Larsson NG, Gustafsson CM
Publication type: Article
Publication status: Published
Journal: Molecular Cell
Year: 2019
Volume: 76
Pages: 1-13
Print publication date: 05/12/2019
Online publication date: 03/10/2019
Acceptance date: 04/09/2019
Date deposited: 03/10/2019
ISSN (print): 1097-2765
ISSN (electronic): 1097-4164
Publisher: Cell Press
URL: https://doi.org/10.1016/j.molcel.2019.09.010
DOI: 10.1016/j.molcel.2019.09.010
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