Functional consequences of bidirectional promoters

Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
Trends in Genetics (Impact Factor: 9.92). 07/2011; 27(7):267-76. DOI: 10.1016/j.tig.2011.04.002
Source: PubMed


Several studies have shown that promoters of protein-coding genes are origins of pervasive non-coding RNA transcription and can initiate transcription in both directions. However, only recently have researchers begun to elucidate the functional implications of this bidirectionality and non-coding RNA production. Increasing evidence indicates that non-coding transcription at promoters influences the expression of protein-coding genes, revealing a new layer of transcriptional regulation. This regulation acts at multiple levels, from modifying local chromatin to enabling regional signal spreading and more distal regulation. Moreover, the bidirectional activity of a promoter is regulated at multiple points during transcription, giving rise to diverse types of transcripts.

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Available from: Vicent Pelechano, Apr 17, 2014
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    • "As the RNA polymerase II (RNAP2) machinery departs the TSS and moves into the gene body, further repositioning of nucleosomes would be necessary, but a key question concerns what happens in the underwound region behind the two RNAP2 complexes? One facet of this question is that this promoter orientation is somehow used to regulate gene expression (Wei et al., 2011). Another facet is that this interplay of transcription, torsional stress, and active chromatin can cause genome instability. "
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    ABSTRACT: The interplay of transcription, topological tension, and chromosome breakage is a subject of intense interest, but, with so many facets to the problem, it is difficult to test. Here, we vary the orientation of promoters relative to one another in a yeast system that permits sensitive detection of chromosome breaks. Interestingly, convergent transcription that would direct RNA polymerases into one another does not increase chromosome breakage. In contrast, divergent transcription that would create underwound and potentially single-stranded DNA does cause a marked increase in chromosome breakage. Furthermore, we examine the role that topoisomerases are playing in preventing genome instability at these promoters and find that Top2 is required to prevent instability at converging promoters.
    Full-text · Article · Jan 2016 · Cell Reports
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    • "On the other hand, addition of a short poly(A) tail is also utilized by the RNA exosome during RNA decay, and thus many decay intermediates as well as noncoding transcripts are terminated by a short poly(A) tail (Wyers et al. 2005; Slomovic et al. 2010). Finally, widespread stutter activity of RNA Pol II surrounding transcriptional start and termination sites (Kapranov et al. 2010; Wei et al. 2011) forms a further source of adenylated RNA in the cell. Here we harness the efficiency of Klenow-mediated 3 ′ tagging (Janicke et al. 2012) to measure the dynamics of the adenylated transcriptome. "
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    ABSTRACT: A major objective of systems biology is to quantitatively integrate multiple parameters from genome-wide measurements. To integrate gene expression with dynamics in poly(A) tail length and adenylation site, we developed a targeted next-generation sequencing approach, Poly(A)-Test RNA-sequencing. PAT-seq returns (i) digital gene expression, (ii) polyadenylation site/s, and (iii) the polyadenylation-state within and between eukaryotic transcriptomes. PAT-seq differs from previous 3' focused RNA-seq methods in that it depends strictly on 3' adenylation within total RNA samples and that the full-native poly(A) tail is included in the sequencing libraries. Here, total RNA samples from budding yeast cells were analyzed to identify the intersect between adenylation state and gene expression in response to loss of the major cytoplasmic deadenylase Ccr4. Furthermore, concordant changes to gene expression and adenylation-state were demonstrated in the classic Crabtree-Warburg metabolic shift. Because all polyadenylated RNA is interrogated by the approach, alternative adenylation sites, noncoding RNA and RNA-decay intermediates were also identified. Most important, the PAT-seq approach uses standard sequencing procedures, supports significant multiplexing, and thus replication and rigorous statistical analyses can for the first time be brought to the measure of 3'-UTR dynamics genome wide. © 2015 Harrison et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.
    Full-text · Article · Jun 2015 · RNA
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    • "Remarkably, fusing the mRNA capping enzymes to a mutant CTD containing all Ser5 residues replaced by Ala was sufficient to restore viability in fission yeast, revealing that, at least in yeast, the main essential function of CTD Ser5 phosphorylation is recruitment of the capping machinery [28]. A surprising discovery from genome-wide analysis was the finding that many genes that are not being expressed contain Pol II initiation complexes engaged with the promoter and may generate short abortive non-coding RNAs that are reminiscent of cryptic unstable transcripts or CUTs [29] [30]. This is the case for genes regulated at specific development stages or inducible genes that need to rapidly respond to specific stimuli. "
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    ABSTRACT: Here we review recent findings showing that chromatin organization adds another layer of complexity to the already intricate network of splicing regulatory mechanisms. Chromatin structure can impact splicing by either affecting the elongation rate of RNA polymerase II or by signaling the recruitment of splicing regulatory proteins. The C-terminal domain of the RNA polymerase II largest subunit serves as a coordination platform that binds factors required for adapting chromatin structure to both efficient transcription and processing of the newly synthesized RNA. Reciprocal interconnectivity of steps required for gene activation plays a critical role ensuring efficiency and fidelity of gene expression.
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