Termination sequence requirements vary among genes transcribed by RNA polymerase III 1 1Edited by J. Karn

Gunnery, Shobha; Ma, Yuliang; Mathews, Michael B.

doi:10.1006/jmbi.1998.2518

Cited by 53 publications

(44 citation statements)

References 30 publications

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“…The T-run length distribution in mammals is completely different: T 4 is the most frequent tDNA terminator, and terminators longer than T 5 are rare. Again, this finding is in agreement with the reported ability of human Pol III (and, more generally, of vertebrate Pols III) to terminate efficiently at T 4 sequences (1,3,18,33).…”

Section: Oligo(dt) Termination Signals In Different Eukaryoticsupporting

confidence: 91%

“…A previously characterized example related to this issue is that of a tRNA Lys gene from Xenopus laevis, in which two T 4 tracts, one located at a canonical downstream position and the other one within the gene itself, determine transcription termination to different extents, with the internal T 4 cluster behaving as a much weaker terminator than the external one (16). The idea that the sequence context can generally influence the efficiency of T clusters first emerged from early studies of Pol III termination (1) and was confirmed and extended by later studies of transcription termination on the adenovirus VA RNA genes (17,18). The surrounding sequences seem to influence Pol III termination especially at short T clusters.…”

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confidence: 97%

“…In Xenopus, for example, only T 4 terminators display a context-dependent strength, whereas clusters of five or more T residues are highly efficient as terminators independently from the context (1). The few documented cases of surrounding sequence effects can hardly be accommodated into general rules of sequence specificity, because the same flanking nucleotides were found to produce different (or even opposite) effects on the terminators of different class III templates (1,16,18). Further adding to the complexity of the sequence requirements for Pol III termination, several observations also suggested the existence of Pol III termination signals that do not conform to the general "T-cluster" rule (18 -20).…”

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confidence: 99%

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Sequence Context Effects on Oligo(dT) Termination Signal Recognition by Saccharomyces cerevisiae RNA Polymerase III

Braglia

Percudani

Dieci

2005

Journal of Biological Chemistry

102

112

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Eukaryotic RNA polymerase (Pol) III terminates transcription at short runs of T residues in the coding DNA strand. By genomic analysis, we found that T 5 and T 4 are the shortest Pol III termination signals in yeasts and mammals, respectively, and that, at variance with yeast, oligo(dT) terminators longer than T 5 are very rare in mammals. In Saccharomyces cerevisiae, the strength of T 5 as a terminator was found to be largely influenced by both the upstream and the downstream sequence context. In particular, the CT sequence, which is naturally present downstream of T 5 in the 3-flank of some tDNAs, was found to act as a terminator-weakening element that facilitates translocation by reducing Pol III pausing at T 5 . In contrast, tDNA transcription termination was highly efficient when T 5 was followed by an A or G residue. Surprisingly, however, when a terminationproficient T 5 signal was taken out from the tDNA context and placed downstream of a fragment of the SCR1 gene, its termination activity was compromised, both in vitro and in vivo. Even the T 6 sequence, acting as a strong terminator in tRNA gene contexts, was unexpectedly weak within the SNR52 transcription unit, where it naturally occurs. The observed sequence context effects reflect intrinsic recognition properties of Pol III, because they were still observed in a simplified in vitro transcription system only consisting of purified RNA polymerase and template DNA. Our findings strengthen the notion that termination signal recognition by Pol III is influenced in a complex way by the region surrounding the T cluster and suggest that read-through transcription beyond T clusters might play a significant role in the biogenesis of class III gene products.Eukaryotic RNA polymerase (Pol) 1 III is unique among DNAdependent RNA polymerases in recognizing a simple run of T residues on the coding strand as a termination signal, in the apparent absence of accessory factors. The minimal signal thought to be sufficient to provoke Pol III termination varies among different eukaryotes. T 4 suffices for termination by Xenopus and human Pol III (1, 2), T 4 /T 5 for Schizosaccharomyces pombe Pol III (3), and T 5 /T 6 for Saccharomyces cerevisiae Pol III (4). Pol III termination within T clusters is generally heterogeneous and progressive (5), and termination efficiency tends to increase with the length of the T run (4). Mechanistically, Pol III termination involves extensive pausing, dictated by the T cluster itself (5, 6). Even during elongation, the addition of three UMP residues in succession is particularly slow (5). Pol III pausing at T clusters sets cycles of hydrolytic RNA chain retraction (7). Both pausing and the associated hydrolytic RNA cleavage are affected by mutations in the C160, C128, and C11 subunits of yeast Pol III (7-9). In the case of C128 and C11, the same mutations have also been shown to affect the termination properties of Pol III, thus suggesting a functional interplay between hydrolytic RNA cleavage and transcription termination (9, 10). The t...

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Section: Oligo(dt) Termination Signals In Different Eukaryoticsupporting

confidence: 91%

mentioning

confidence: 97%

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confidence: 99%

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Sequence Context Effects on Oligo(dT) Termination Signal Recognition by Saccharomyces cerevisiae RNA Polymerase III

Braglia

Percudani

Dieci

2005

Journal of Biological Chemistry

102

112

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“…RNAPIII recycling is also dependent on a natural termination signal (Dieci and Sentenac 1996;Ferrari et al 2004). Termination can be influenced by sequences surrounding the T tract (Bogenhagen and Brown 1981;Mazabraud et al 1987;Gunnery et al 1999;Braglia et al 2005). Braglia et al (2005) proposed that the surrounding residues and, in particular, downstream residues of the yeast terminator influence the pausing time or the processivity of RNA-PIII.…”

Section: Rnapiii: a Terminator On Its Own?mentioning

confidence: 99%

Transcription termination by nuclear RNA polymerases

Richard

Manley²

2009

Genes Dev.

289

326

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Gene transcription in the cell nucleus is a complex and highly regulated process. Transcription in eukaryotes requires three distinct RNA polymerases, each of which employs its own mechanisms for initiation, elongation, and termination. Termination mechanisms vary considerably, ranging from relatively simple to exceptionally complex. In this review, we describe the present state of knowledge on how each of the three RNA polymerases terminates and how mechanisms are conserved, or vary, from yeast to human.

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“…However, their delivery strategies did not target a specific cell population due to the ubiquitous existence of Pol-III activity in all cell types. Because the readthrough side-effect of Pol-III occurs on a short transcription template if without proper termination, large RNA products longer than desired 18-25 base-pairs (bp) can be synthesized and then cause unexpected interferon cytotoxicity [40,41]. Such a problem can also result from the competitive conflict between the Pol-III promoter and another vector promoter (i.e.…”

Section: Advantages Of Mirna-mediated Rnai Mechanismmentioning

confidence: 99%

Current perspectives in intronic micro RNAs (miRNAs)

Ying

Lin

2005

J Biomed Sci

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SummaryMicroRNAs (miRNAs), small single-stranded regulatory RNAs capable of interfering with intracellular messenger RNAs (mRNAs) that contain either complete or partial complementarity, are useful for the design of new therapies against cancer polymorphism and viral mutation. Numerous miRNAs have been reported to induce RNA interference (RNAi), a post-transcriptional gene silencing mechanism. Intronic miRNAs, derived from introns by RNA splicing and Dicer processing, can interfere with intracellular mRNAs to silence that gene expression. The intronic miRNAs differ uniquely from previously described intergenic miRNAs in the requirement of type II RNA polymerases (Pol-II) and spliceosomal components for its biogenesis. Several kinds of intronic miRNAs have been identified in Caenorhabditis elegans, mouse and human cells; however, neither their function nor application has been reported. To this day, the computer searching program for miRNA seldom include the intronic portion of protein-coding RNAs. The functional significance of artificially generated intronic miRNAs has been successfully ascertained in several biological systems such as zebrafishes, chicken embryos and adult mice, indicating the evolutionary preservation of this gene regulation system in vivo. Multiple miRNAs can be generated from the same cluster of introns; however, non-homologous miRNAs may have different targets and functions while homologous miRNA may be derived from different intronic clusters. Taken together, the model of intronic miRNAmediated transgenic animals provides a tool to investigate the mechanism of miRNA-associated diseases in vivo and will shed light on miRNA-related therapies.

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Termination sequence requirements vary among genes transcribed by RNA polymerase III 1 1Edited by J. Karn

Cited by 53 publications

References 30 publications

Sequence Context Effects on Oligo(dT) Termination Signal Recognition by Saccharomyces cerevisiae RNA Polymerase III

Sequence Context Effects on Oligo(dT) Termination Signal Recognition by Saccharomyces cerevisiae RNA Polymerase III

Transcription termination by nuclear RNA polymerases

Current perspectives in intronic micro RNAs (miRNAs)

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