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Dinucleotide Degradation by REXO2 Maintains Promoter Specificity in Mammalian Mitochondria

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 sub...

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Autores principales: Nicholls, Thomas J., Spåhr, Henrik, Jiang, Shan, Siira, Stefan J., Koolmeister, Camilla, Sharma, Sushma, Kauppila, Johanna H.K., Jiang, Min, Kaever, Volkhard, Rackham, Oliver, Chabes, Andrei, Falkenberg, Maria, Filipovska, Aleksandra, Larsson, Nils-Göran, Gustafsson, Claes M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900737/
https://www.ncbi.nlm.nih.gov/pubmed/31588022
http://dx.doi.org/10.1016/j.molcel.2019.09.010
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author Nicholls, Thomas J.
Spåhr, Henrik
Jiang, Shan
Siira, Stefan J.
Koolmeister, Camilla
Sharma, Sushma
Kauppila, Johanna H.K.
Jiang, Min
Kaever, Volkhard
Rackham, Oliver
Chabes, Andrei
Falkenberg, Maria
Filipovska, Aleksandra
Larsson, Nils-Göran
Gustafsson, Claes M.
author_facet Nicholls, Thomas J.
Spåhr, Henrik
Jiang, Shan
Siira, Stefan J.
Koolmeister, Camilla
Sharma, Sushma
Kauppila, Johanna H.K.
Jiang, Min
Kaever, Volkhard
Rackham, Oliver
Chabes, Andrei
Falkenberg, Maria
Filipovska, Aleksandra
Larsson, Nils-Göran
Gustafsson, Claes M.
author_sort Nicholls, Thomas J.
collection PubMed
description 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.
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spelling pubmed-69007372020-01-21 Dinucleotide Degradation by REXO2 Maintains Promoter Specificity in Mammalian Mitochondria Nicholls, Thomas J. Spåhr, Henrik Jiang, Shan Siira, Stefan J. Koolmeister, Camilla Sharma, Sushma Kauppila, Johanna H.K. Jiang, Min Kaever, Volkhard Rackham, Oliver Chabes, Andrei Falkenberg, Maria Filipovska, Aleksandra Larsson, Nils-Göran Gustafsson, Claes M. Mol Cell Article 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. Cell Press 2019-12-05 /pmc/articles/PMC6900737/ /pubmed/31588022 http://dx.doi.org/10.1016/j.molcel.2019.09.010 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Nicholls, Thomas J.
Spåhr, Henrik
Jiang, Shan
Siira, Stefan J.
Koolmeister, Camilla
Sharma, Sushma
Kauppila, Johanna H.K.
Jiang, Min
Kaever, Volkhard
Rackham, Oliver
Chabes, Andrei
Falkenberg, Maria
Filipovska, Aleksandra
Larsson, Nils-Göran
Gustafsson, Claes M.
Dinucleotide Degradation by REXO2 Maintains Promoter Specificity in Mammalian Mitochondria
title Dinucleotide Degradation by REXO2 Maintains Promoter Specificity in Mammalian Mitochondria
title_full Dinucleotide Degradation by REXO2 Maintains Promoter Specificity in Mammalian Mitochondria
title_fullStr Dinucleotide Degradation by REXO2 Maintains Promoter Specificity in Mammalian Mitochondria
title_full_unstemmed Dinucleotide Degradation by REXO2 Maintains Promoter Specificity in Mammalian Mitochondria
title_short Dinucleotide Degradation by REXO2 Maintains Promoter Specificity in Mammalian Mitochondria
title_sort dinucleotide degradation by rexo2 maintains promoter specificity in mammalian mitochondria
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900737/
https://www.ncbi.nlm.nih.gov/pubmed/31588022
http://dx.doi.org/10.1016/j.molcel.2019.09.010
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