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Mutations of RNA polymerase II activate key genes of the nucleoside triphosphate biosynthetic pathways
The yeast URA2 gene, encoding the rate-limiting enzyme of UTP biosynthesis, is transcriptionally activated by UTP shortage. In contrast to other genes of the UTP pathway, this activation is not governed by the Ppr1 activator. Moreover, it is not due to an increased recruitment of RNA polymerase II a...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2525842/ https://www.ncbi.nlm.nih.gov/pubmed/18716630 http://dx.doi.org/10.1038/emboj.2008.165 |
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author | Kwapisz, Marta Wery, Maxime Després, Daphné Ghavi-Helm, Yad Soutourina, Julie Thuriaux, Pierre Lacroute, François |
author_facet | Kwapisz, Marta Wery, Maxime Després, Daphné Ghavi-Helm, Yad Soutourina, Julie Thuriaux, Pierre Lacroute, François |
author_sort | Kwapisz, Marta |
collection | PubMed |
description | The yeast URA2 gene, encoding the rate-limiting enzyme of UTP biosynthesis, is transcriptionally activated by UTP shortage. In contrast to other genes of the UTP pathway, this activation is not governed by the Ppr1 activator. Moreover, it is not due to an increased recruitment of RNA polymerase II at the URA2 promoter, but to its much more effective progression beyond the URA2 mRNA start site(s). Regulatory mutants constitutively expressing URA2 resulted from cis-acting deletions upstream of the transcription initiator region, or from amino-acid replacements altering the RNA polymerase II Switch 1 loop domain, such as rpb1-L1397S. These two mutation classes allowed RNA polymerase to progress downstream of the URA2 mRNA start site(s). rpb1-L1397S had similar effects on IMD2 (IMP dehydrogenase) and URA8 (CTP synthase), and thus specifically activated the rate-limiting steps of UTP, GTP and CTP biosynthesis. These data suggest that the Switch 1 loop of RNA polymerase II, located at the downstream end of the transcription bubble, may operate as a specific sensor of the nucleoside triphosphates available for transcription. |
format | Text |
id | pubmed-2525842 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-25258422008-08-27 Mutations of RNA polymerase II activate key genes of the nucleoside triphosphate biosynthetic pathways Kwapisz, Marta Wery, Maxime Després, Daphné Ghavi-Helm, Yad Soutourina, Julie Thuriaux, Pierre Lacroute, François EMBO J Article The yeast URA2 gene, encoding the rate-limiting enzyme of UTP biosynthesis, is transcriptionally activated by UTP shortage. In contrast to other genes of the UTP pathway, this activation is not governed by the Ppr1 activator. Moreover, it is not due to an increased recruitment of RNA polymerase II at the URA2 promoter, but to its much more effective progression beyond the URA2 mRNA start site(s). Regulatory mutants constitutively expressing URA2 resulted from cis-acting deletions upstream of the transcription initiator region, or from amino-acid replacements altering the RNA polymerase II Switch 1 loop domain, such as rpb1-L1397S. These two mutation classes allowed RNA polymerase to progress downstream of the URA2 mRNA start site(s). rpb1-L1397S had similar effects on IMD2 (IMP dehydrogenase) and URA8 (CTP synthase), and thus specifically activated the rate-limiting steps of UTP, GTP and CTP biosynthesis. These data suggest that the Switch 1 loop of RNA polymerase II, located at the downstream end of the transcription bubble, may operate as a specific sensor of the nucleoside triphosphates available for transcription. Nature Publishing Group 2008-09-17 2008-08-21 /pmc/articles/PMC2525842/ /pubmed/18716630 http://dx.doi.org/10.1038/emboj.2008.165 Text en Copyright © 2008, European Molecular Biology Organization http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This licence does not permit commercial exploitation without specific permission. |
spellingShingle | Article Kwapisz, Marta Wery, Maxime Després, Daphné Ghavi-Helm, Yad Soutourina, Julie Thuriaux, Pierre Lacroute, François Mutations of RNA polymerase II activate key genes of the nucleoside triphosphate biosynthetic pathways |
title | Mutations of RNA polymerase II activate key genes of the nucleoside triphosphate biosynthetic pathways |
title_full | Mutations of RNA polymerase II activate key genes of the nucleoside triphosphate biosynthetic pathways |
title_fullStr | Mutations of RNA polymerase II activate key genes of the nucleoside triphosphate biosynthetic pathways |
title_full_unstemmed | Mutations of RNA polymerase II activate key genes of the nucleoside triphosphate biosynthetic pathways |
title_short | Mutations of RNA polymerase II activate key genes of the nucleoside triphosphate biosynthetic pathways |
title_sort | mutations of rna polymerase ii activate key genes of the nucleoside triphosphate biosynthetic pathways |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2525842/ https://www.ncbi.nlm.nih.gov/pubmed/18716630 http://dx.doi.org/10.1038/emboj.2008.165 |
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