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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2019
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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. |
format | Online Article Text |
id | pubmed-6900737 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
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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