Role of transcriptional interference in the Drosophila melanogaster Adh promoter switch

Corbin, Victoria; Maniatis, Tom

doi:10.1038/337279a0

Cited by 142 publications

(121 citation statements)

References 23 publications

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“…The proximal promoter is active in first-to early third-instar larvae. The distal promoter then turns on and represses the proximal promoter by transcribing through it (Corbin and Maniatis 1989).…”

Section: Terminator-promoter Interactions On Genes Transcribed By Rnamentioning

confidence: 99%

An RNA polymerase I termination site can stimulate the adjacent ribosomal gene promoter by two distinct mechanisms in Xenopus laevis.

McStay

Reeder²

1990

Genes Dev.

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On the ribosomal genes of Xenopus laevis, the T3 terminator is located -60 bp upstream of the 5' boundary of the gene promoter. We have shown previously that mutation of the terminator simultaneously abolishes termination and impairs initiation by RNA polymerase I. Here, we show that the terminator influences the promoter by two distinct mechanisms. In one mechanism the terminator protects the promoter by preventing polymerase from reading through the initiation complex. In a second mechanism, the terminator interacts directly with the promoter, whether or not termination occurs. This positive interaction requires precise positioning of the terminator relative to the promoter and is sensitive to movement of the terminator by as little as 1 or 2 bp. We conclude that the terminator and promoter interact as one interdependent complex.

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Section: Terminator-promoter Interactions On Genes Transcribed By Rnamentioning

confidence: 99%

An RNA polymerase I termination site can stimulate the adjacent ribosomal gene promoter by two distinct mechanisms in Xenopus laevis.

McStay

Reeder²

1990

Genes Dev.

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“…6). The two transcripts are initiated from separate promoters, each having its own enhancer sequence (7). Transcripts from a proximal promoter are found predominantly in larvae, while transcripts from a distal promoter are found predominantly in adult flies (6).…”

mentioning

confidence: 99%

“…Transcripts from a proximal promoter are found predominantly in larvae, while transcripts from a distal promoter are found predominantly in adult flies (6). P-element-mediated transformation experiments have shown that all of the cis-acting sequence elements required for proper Adh expression are contained within a 8.6-kb SacI-ClaI genomic Adh fragment (7,8) and that a single replacement substitution can alter the catalytic efficiency of the alcohol dehydrogenase (ADH) enzyme (9). In addition, it has been demonstrated that nonreplacement sites must also play a role in determining the level of Adh expression (9, 10).…”

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confidence: 99%

Site-directed mutations reveal long-range compensatory interactions in the Adh gene of Drosophila melanogaster

Parsch

Tanda

Stephan

1997

Proc. Natl. Acad. Sci. U.S.A.

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Long-range interactions between the 5 and 3 ends of mRNA molecules have been suggested to play a role in the initiation of translation and the regulation of gene expression. To identify such interactions and to study their molecular evolution, we used phylogenetic analysis to generate a model of mRNA higher-order structure in the Adh transcript of Drosophila melanogaster. This model predicts long-range, tertiary contacts between a region of the protein-encoding sequence just downstream of the start codon and a conserved sequence in the 3 untranslated region (UTR). To further examine the proposed structure, site-directed mutations were generated in vitro in a cloned D. melanogaster Adh gene, and the mutant constructs were introduced into the Drosophila germ line through P-element mediated transformation. Transformants were spectrophotometrically assayed for alcohol dehydrogenase activity. Our results indicate that transformants containing a silent mutation near the start of the proteinencoding sequence show an Ϸ15% reduction in alcohol dehydrogenase activity relative to wild-type transformants. This activity can be restored to wild-type levels by a second, compensatory mutation in the 3 UTR. These observations are consistent with a higher-order structure model that includes long-range interactions between the 5 and 3 ends of the Adh mRNA. However, our results do not fit the classical compensatory substitution model because the second mutation by itself (in the 3 UTR) did not show a measurable reduction in gene expression.There is a growing body of evidence for functional, long-range interactions between the 5Ј and 3Ј ends of eukaryotic mRNA molecules. Tarun and Sachs (1) have shown that a protein which binds to the 3Ј end of yeast mRNA is involved in the initiation of translation which occurs at the 5Ј end. Similarly, in Drosophila, proteins that bind to an mRNA's 3Ј untranslated region (UTR) have been shown to affect levels of translation (2, 3). In addition to these studies of protein-protein interactions, several sources have suggested direct RNA-RNA pairings between the two ends of mRNA molecules. Konings et al. (4) used a free-energy minimization algorithm to predict folding patterns for 38 eukaryotic mRNAs. Their results indicate a common pattern of mRNA folding, where the 3Ј UTR forms contacts with the coding region just downstream of the start codon. Stephan and Kirby (5) used a phylogenetic comparison method to predict mRNA secondary structures in Drosophila and found evidence for long-range pairings between the 3Ј UTR and the protein-encoding region. These findings raise a number of important questions. For instance, which nucleotides are involved in RNA-RNA interactions and how are they arranged into secondary and tertiary pairing regions? Do the currently available models describe the evolution of compensatory mutations adequately? To begin to address these questions, we have focused on identifying elements of the Adh mRNA higher-order structure in Drosophila melanogaster.Adh produces two deve...

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“…At this time transcription switches to the distal transcript until the beginning of the pupa stage, although the level of transcription is much lower than it had been for the proximal transcript (Corbin & Maniatis, 1989). In adult flies the distal transcript is the major form.…”

Section: Introductionmentioning

confidence: 99%

A Tirant insertion in the alcohol dehydrogenase locus of Drosophila melanogaster

Gibson

1998

Heredity

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An alcohol dehydrogenase allele Adh AAS44 isolated from an Australian natural population of Drosophila melanogaster is associated with low activity in adult flies. A 5.0 kb insertion in the first intron between the distal and proximal promoters has been partially sequenced and shown to be homologous to the retrotransposon Tirant. The insertion is the major change in the transcriptional unit of Adh AAS44 , but there is also a single nucleotide change in the adult Adh enhancer. The main phenotypic effect associated with the Tirant insertion is a reduction in alcohol dehydrogenase activity and transcript level in adult flies. There is a very much smaller reduction in 3rd instar larvae. The data indicate that Tirant affects transcription from the distal promoter. The possible mechanisms for this differential effect on transcription are discussed.

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Role of transcriptional interference in the Drosophila melanogaster Adh promoter switch

Cited by 142 publications

References 23 publications

An RNA polymerase I termination site can stimulate the adjacent ribosomal gene promoter by two distinct mechanisms in Xenopus laevis.

An RNA polymerase I termination site can stimulate the adjacent ribosomal gene promoter by two distinct mechanisms in Xenopus laevis.

Site-directed mutations reveal long-range compensatory interactions in the Adh gene of Drosophila melanogaster

A Tirant insertion in the alcohol dehydrogenase locus of Drosophila melanogaster

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