Mutations of RNA polymerase II activate key genes of the nucleoside triphosphate biosynthetic pathways.
EMBO J
; 27(18): 2411-21, 2008 Sep 17.
Article
em En
| MEDLINE
| ID: mdl-18716630
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Aspartato Carbamoiltransferase
/
RNA Polimerase II
/
Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)
/
Regulação da Expressão Gênica
/
Proteínas de Saccharomyces cerevisiae
/
Mutação
/
Nucleosídeos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
França