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Dinucleotide Degradation by REXO2 Maintains Promoter Specificity in Mammalian Mitochondria
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2019 (English)In: Molecular Cell, ISSN 1097-2765, E-ISSN 1097-4164, Vol. 76, no 5, p. 784-+Article in journal (Refereed) Published
Abstract [en]

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. Here we demonstrate that REXO2 is a specialized 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.

Place, publisher, year, edition, pages
Elsevier, 2019. Vol. 76, no 5, p. 784-+
National Category
Biochemistry and Molecular Biology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-166839DOI: 10.1016/j.molcel.2019.09.010ISI: 000500937100010PubMedID: 31588022OAI: oai:DiVA.org:umu-166839DiVA, id: diva2:1382333
Funder
Swedish Research Council, 2015-00418Swedish Research Council, 2018-02439Swedish Research Council, 2018-02579Swedish Research Council, 2017-01257Swedish Cancer Society, 2016-816Swedish Cancer Society, 2016-599Swedish Cancer Society, 2017-631Swedish Cancer Society, 2018-602Knut and Alice Wallenberg Foundation, KAW 2017.0080Knut and Alice Wallenberg Foundation, KAW 2016.0050Wellcome trust, 213464/Z/18/ZAvailable from: 2020-01-02 Created: 2020-01-02 Last updated: 2020-01-02Bibliographically approved

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Sharma, SushmaChabes, Andrei

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Nicholls, Thomas J.Jiang, ShanSharma, SushmaRackham, OliverChabes, Andrei
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