Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript
| Autor: | Alexandre Akoulitchev, Natalie Chow, Aroul Ramadass, Igor Martianov, Ana Serra Barros |
|---|---|
| Přispěvatelé: | Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
RNA
Untranslated Transcription Genetic RNA-induced transcriptional silencing MESH: TATA-Box Binding Protein RNA polymerase II MESH: Tetrahydrofolate Dehydrogenase Gene Expression Regulation Enzymologic Substrate Specificity MESH: RNA Untranslated 03 medical and health sciences 0302 clinical medicine Transcription (biology) Gene expression MESH: Epistasis Genetic Humans MESH: Gene Silencing Gene Silencing Promoter Regions Genetic 030304 developmental biology 0303 health sciences Multidisciplinary MESH: Humans biology General transcription factor MESH: Gene Expression Regulation Enzymologic MESH: Transcription Genetic MESH: Transcription Factor TFIIB RNA Epistasis Genetic [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology TATA-Box Binding Protein Molecular biology Tetrahydrofolate Dehydrogenase RNA silencing MESH: Promoter Regions (Genetics) 030220 oncology & carcinogenesis Transcription Factor TFIIB biology.protein Transcription factor II F MESH: Substrate Specificity |
| Zdroj: | Nature Nature, Nature Publishing Group, 2007, 445 (7128), pp.666-70. ⟨10.1038/nature05519⟩ |
| ISSN: | 0028-0836 1476-4679 |
| DOI: | 10.1038/nature05519⟩ |
| Popis: | In recent years it has become clear that non-coding RNAs (that is, RNAs that are not translated into proteins) play a vital role in regulating gene expression. A previously unknown manifestation of that control has been found to operate on the human dihydrofolate reductase (DHFR) gene. The interfering RNA forms a complex with the DHFR gene's promoter region, and in so doing it interferes with the binding of transcription factors. The non-coding RNA is produced only in quiescent cells, leading to repression of the DHFR gene in these conditions. The DHFR major promoter is repressed in quiescent cells by a non-coding RNA initiated from an upstream promoter. This RNA molecule forms a complex with the major promoter, interacts with the general transcription factor IIB, and dissociates the pre-initiation complex from the promoter. Alternative promoters within the same gene are a general phenomenon in gene expression1,2. Mechanisms of their selective regulation vary from one gene to another and are still poorly understood. Here we show that in quiescent cells the mechanism of transcriptional repression of the major promoter of the gene encoding dihydrofolate reductase depends on a non-coding transcript initiated from the upstream minor promoter and involves both the direct interaction of the RNA and promoter-specific interference. The specificity and efficiency of repression is ensured by the formation of a stable complex between non-coding RNA and the major promoter, direct interaction of the non-coding RNA with the general transcription factor IIB and dissociation of the preinitiation complex from the major promoter. By using in vivo and in vitro assays such as inducible and reconstituted transcription, RNA bandshifts, RNA interference, chromatin immunoprecipitation and RNA immunoprecipitation, we show that the regulatory transcript produced from the minor promoter has a critical function in an epigenetic mechanism of promoter-specific transcriptional repression. |
| Databáze: | OpenAIRE |
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