Regulation of gene expression by reiterative transcription

Turnbough, Charles L.

doi:10.1016/j.mib.2011.01.012

Cited by 33 publications

(53 citation statements)

References 39 publications

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“…Changes in the slippage rates might also influence gene expression levels by altering the efficiency of promoter escape or termination (35). The growth rates of the slippage-prone mutants are generally slower than the WT strain with the rpb1-S751F allele, causing the most severe growth defect.…”

Section: Met-487mentioning

confidence: 99%

The Fidelity of Transcription

Strathern

Malagón

Irvin

et al. 2013

Journal of Biological Chemistry

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Background: Yeast RNA polymerase II domains involved in maintenance of transcription register are unknown. Results: We isolated and biochemically characterized RPB1 mutations leading to register loss (transcription slippage). Conclusion: All RPB1 mutations affect slippage localize close to the active center and near the secondary pore of RNA polymerase II. Significance: Our results shed light on the mechanism of slippage by eukaryotic RNA polymerases.

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Section: Met-487mentioning

confidence: 99%

The Fidelity of Transcription

Strathern

Malagón

Irvin

et al. 2013

Journal of Biological Chemistry

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“…Our comparisons of the resulting promoters suggest that the importance of start site sequence is, at least in large part, its contribution to the base-pairing strength of the RNA-DNA hybrid formed by the first 4 or 5 residues at the 5= end of the nascent transcript and the DNA template. Previous studies had, in fact, demonstrated that weak RNA-DNA base pairing facilitates reiterative transcription during transcription initiation and elongation (3,11,32,33). Using different promoter contexts, we showed that an RNA-DNA hybrid containing the 5=-AUUU transcript allowed more extensive reiterative transcription, especially at high UTP concentrations, than that observed with stronger hybrids formed with 5=-GUUU and 5=-AAUUU transcripts.…”

Section: Discussionmentioning

confidence: 57%

“…During initiation, when the length of the RNA-DNA hybrid can be shorter than that of the 8-to 9-bp hybrid that forms during elongation (8), a homopolymeric tract as short as three residues can enable reiterative transcription (9, 10). In contrast, longer homopolymeric tracts usually are required for reiterative transcription during elongation and termination (6, 7).The physiological significance of reiterative transcription is that it plays a central role in regulating the expression of numerous prokaryotic, viral, and eukaryotic genes through an assortment of different mechanisms (3,11). In Escherichia coli, expression of at least five operons is regulated by mechanisms involving the reiterative addition of U residues during transcription initiation (4,(12)(13)(14)(15).…”

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confidence: 99%

“…The physiological significance of reiterative transcription is that it plays a central role in regulating the expression of numerous prokaryotic, viral, and eukaryotic genes through an assortment of different mechanisms (3,11). In Escherichia coli, expression of at least five operons is regulated by mechanisms involving the reiterative addition of U residues during transcription initiation (4,(12)(13)(14)(15).…”

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confidence: 99%

“…In Escherichia coli, expression of at least five operons is regulated by mechanisms involving the reiterative addition of U residues during transcription initiation (4,(12)(13)(14)(15). Although these mechanisms can differ fundamentally (11), three examples include analogous mechanisms that regulate, in part, the expression of the pyrBI and carAB pyrimidine nucleotide biosynthetic operons and the galETKM (gal) galactose catabolic operon (12)(13)(14). The promoters of each of these operons (at least one when there are multiple promoters) include initially transcribed regions that contain a tract of three T·A base pairs located one or two bases downstream from the transcription start site (Fig.…”

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Transcription Start Site Sequence and Spacing between the −10 Region and the Start Site Affect Reiterative Transcription-Mediated Regulation of Gene Expression in Escherichia coli

Han

Turnbough

2014

J Bacteriol

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Reiterative transcription is a reaction catalyzed by RNA polymerase, in which nucleotides are repetitively added to the 3= end of a nascent transcript due to upstream slippage of the transcript without movement of the DNA template. In Escherichia coli, the expression of several operons is regulated through mechanisms in which high intracellular levels of UTP promote reiterative transcription that adds extra U residues to the 3= end of a nascent transcript during transcription initiation. Immediately following the addition of one or more extra U residues, the nascent transcripts are released from the transcription initiation complex, thereby reducing the level of gene expression. Therefore, gene expression can be regulated by internal UTP levels, which reflect the availability of external pyrimidine sources. The magnitude of gene regulation by these mechanisms varies considerably, even when control mechanisms are analogous. These variations apparently are due to differences in promoter sequences. One of the operons regulated (in part) by UTP-sensitive reiterative transcription in E. coli is the carAB operon, which encodes the first enzyme in the pyrimidine nucleotide biosynthetic pathway. In this study, we used the carAB operon to examine the effects of nucleotide sequence at and near the transcription start site and spacing between the start site and ؊10 region of the promoter on reiterative transcription and gene regulation. Our results indicate that these variables are important determinants in establishing the extent of reiterative transcription, levels of productive transcription, and range of gene regulation. Usually during transcription, the nascent RNA transcript and the template strand of DNA move in tandem as an RNA-DNA hybrid. However, during transcription of a homopolymeric tract in the DNA template, the nascent transcript can slip (typically) one base upstream without movement of the DNA template within the active site of RNA polymerase (RNAP) (1, 2). This repositioning allows the same template base to specify an additional nucleotide in the transcript, and when transcript slippage occurs repetitively, the same template nucleotide can specify multiple extra residues. This reaction is called reiterative transcription (also known as RNAP stuttering, transcription slippage, and pseudotemplated transcription) and appears to be catalyzed by all RNAPs (2-5). Reiterative transcription can involve the repetitive addition of any of the four nucleoside triphosphate substrates and occurs during transcription initiation, elongation, and termination (2, 3, 6, 7). During initiation, when the length of the RNA-DNA hybrid can be shorter than that of the 8-to 9-bp hybrid that forms during elongation (8), a homopolymeric tract as short as three residues can enable reiterative transcription (9, 10). In contrast, longer homopolymeric tracts usually are required for reiterative transcription during elongation and termination (6, 7).The physiological significance of reiterative transcription is that it plays a central rol...

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Slippage at the initiation of RNA synthesis by Qβ replicase results in a periodic polyG pattern

2022

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The repetitive copying of template nucleotides due to transcriptional slippage has not been reported for RNA‐directed RNA polymerases of positive‐strand RNA phages. We unexpectedly observed that, with GTP as the only substrate, Qβ replicase, the RNA‐directed RNA polymerase of bacteriophage Qβ, synthesizes by transcriptional slippage polyG strands, which on denaturing electrophoresis produce a ladder with at least three clusters of bolder bands. The ≈ 15‐nt‐long G15, the major product of the shortest cluster, is tightly bound by the enzyme but can be released by the ribosomal protein S1, which, as a Qβ replicase subunit, normally promotes the release of a completed transcript. 7‐deaza‐GTP suppresses the polyG synthesis and abolishes the periodic pattern, suggesting that the N7 atom is needed for the initiation of RNA synthesis and the formation of the structure recognized by protein S1. The results provide new insights into the mechanism of RNA synthesis by the RNA‐directed RNA polymerase of a single‐stranded RNA phage.

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Regulation of gene expression by reiterative transcription

Cited by 33 publications

References 39 publications

The Fidelity of Transcription

The Fidelity of Transcription

Transcription Start Site Sequence and Spacing between the −10 Region and the Start Site Affect Reiterative Transcription-Mediated Regulation of Gene Expression in Escherichia coli

Slippage at the initiation of RNA synthesis by Qβ replicase results in a periodic polyG pattern

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