Polycomb proteins form chromatin-modifying complexes that implement transcriptional silencing in higher eukaryotes. Hundreds of genes are silenced by Polycomb proteins, including dozens of genes that encode crucial de...
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Polycomb proteins form chromatin-modifying complexes that implement transcriptional silencing in higher eukaryotes. Hundreds of genes are silenced by Polycomb proteins, including dozens of genes that encode crucial developmental regulators in organisms ranging from plants to humans. Two main families of complexes, called Polycomb repressive complex 1 (PRC1) and PRC2, are targeted to repressed regions. Recent studies have advanced our understanding of these complexes, including their potential mechanisms of gene silencing, the roles of chromatin modifications, their means of delivery to target genes and the functional distinctions among variant complexes. Emerging concepts include the existence of a Polycomb barrier to transcription elongation and the involvement of non-coding rnas in the targeting of Polycomb complexes. These findings have an impact on the epigenetic programming of gene expression in many biological systems.
Kaposi's sarcoma-associated herpesvirus (KSHV), also designated human herpesvirus 8 (HHV-8), has been linked to Kaposi's sarcoma, as well as to primary effusion lymphoma (PEL), and a subset of multicentric Cas...
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Kaposi's sarcoma-associated herpesvirus (KSHV), also designated human herpesvirus 8 (HHV-8), has been linked to Kaposi's sarcoma, as well as to primary effusion lymphoma (PEL), and a subset of multicentric Castleman's disease. KSHV genomes are maintained as episomes within infected cells and the virus exhibits a biphasic life cycle consisting of a life-long latent phase during which only a few viral genes are expressed and no viral progeny are produced and a transient lytic reactivation phase, in which a full repertoire of 80 lytic genes are activated in a temporally regulated manner culminating in the release of new virions. Lytic replication is initiated by a single viral protein, K-Rta (ORF50), which activates more than 80 viral genes from multiple resident viral episomes (i.e., viral chromosomes). One of the major targets of K-Rta is a long non-coding nuclear rna, PAN rna (polyadenylated nuclear rna), a lncrna that accumulates to exceedingly high levels in the nucleus during viral reactivation. K-Rta directly binds to the PAN rna promoter and robustly activates PAN rna expression. Although PAN rna has been known for over 20 years, its role in viral replication is still incompletely understood. In this perspective, we will briefly review the current understanding of PAN rna and then describe our current working model of this rna. The model is based on our observations concerning events that occur during KSHV lytic reactivation including (i) a marked accumulation of rna Pol II at the PAN promoter, (ii) genomic looping emanating from the PAN locus, (iii) interaction of a second viral lytic protein (ORF57) with K-Rta, PAN rna and rna Pol II, (iv) the essential requirement for PAN rna expression in cis for optimal transcriptional execution needed for the entire lytic program, and (v) ORF57 recruitment of rna Pol II to the PAN genomic locus. Together our results generate a model in which the PAN locus serves as a hub for sequestration/trapping of the cellular transcri
In Pseudomonas aeruginosa carbon catabolite repression (CCR) is exerted by the CbrA/B-CrcZ-Crc global regulatory system. Crc is a translational repressor that, in the presence of preferred carbon sources, such as C4-d...
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In Pseudomonas aeruginosa carbon catabolite repression (CCR) is exerted by the CbrA/B-CrcZ-Crc global regulatory system. Crc is a translational repressor that, in the presence of preferred carbon sources, such as C4-dicarboxylates, impairs the utilization of less preferred substrates. When non-preferred substrates are present, the CrcZ srna levels increase leading to Crc capture, thereby allowing growth of the bacterium at the expense of the non-preferred substrates. The C4-dicarboxylate transport (Dct) system in *** is composed of two main transporters: DctA, more efficient at mM succinate concentrations, and DctPQM, more important at M. In this study, we demonstrate that the Dct transporters are differentially regulated by Crc, depending on the concentration of succinate. At high concentrations, Crc positively regulates the expression of the dctA transporter gene and negatively regulates dctPQM post-transcriptionally. The activation of dctA is explained by a Crc-mediated repression of dctR, encoding a transcriptional repressor of dctA. At low succinate concentrations, Crc regulation is impaired. In this condition, CrcZ levels are higher and therefore more Crc proteins are sequestered, decreasing the amount of Crc available to perform CCR on dctR and dctPQM. As a result, expression of dctA is reduced and that of dctPQM is increased.
Introduction: An important trend in vaccinology is the development of oral vaccines based on genetically modified *** covered: Several studies have suggested that dietary micrornas from plants and other organisms are ...
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Introduction: An important trend in vaccinology is the development of oral vaccines based on genetically modified *** covered: Several studies have suggested that dietary micrornas from plants and other organisms are bioavailable upon oral ingestion exerting biological events in the host such as the modulation of gene expression in several cell types. Since oral plant-based vaccines rely on whole cells as vaccine delivery vehicles, mirnas could play a role in the immunogenic activity of this type of vaccine. In the present report, this hypothesis is discussed under the light of recent evidence on the immunomodulatory activity exerted by mirnas using in vitro and in vivo *** commentary: The ways to generate new knowledge and exploit the potential of mirnas in the development of oral vaccines are discussed.
The Xist long noncodingrna orchestrates X chromosome inactivation, a process that entails chromosome-wide silencing and remodeling of the three-dimensional (3D) structure of the X chromosome. Yet, it remains unclear ...
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The Xist long noncodingrna orchestrates X chromosome inactivation, a process that entails chromosome-wide silencing and remodeling of the three-dimensional (3D) structure of the X chromosome. Yet, it remains unclear whether these changes in nuclear structure are mediated by Xist and whether they are required for silencing. Here, we show that Xist directly interacts with the Lamin B receptor, an integral component of the nuclear lamina, and that this interaction is required for Xist-mediated silencing by recruiting the inactive X to the nuclear lamina and by doing so enables Xist to spread to actively transcribed genes across the X. Our results demonstrate that lamina recruitment changes the 3D structure of DNA, enabling Xist and its silencing proteins to spread across the X to silence transcription.
High-throughput rna sequencing has unveiled the existence of a large number of noncoding antisense rnas derived from bidirectional promoters;unlike sense transcripts, these rnas are often unstable. Two recent reports ...
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High-throughput rna sequencing has unveiled the existence of a large number of noncoding antisense rnas derived from bidirectional promoters;unlike sense transcripts, these rnas are often unstable. Two recent reports investigate why downstream transcription is productive, whereas upstream transcripts are prone to degradation, revealing that an asymmetric distribution of polyadenylation signals and U1 snRNP-binding sites surrounding transcription start sites control the outcome of bidirectional transcription.
MOTIVATION: Evolutionary expansion of gene regulatory circuits seems to boost morphological complexity. However, the expansion patterns and the quantification relationships have not yet been identified. In this study,...
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MOTIVATION: Evolutionary expansion of gene regulatory circuits seems to boost morphological complexity. However, the expansion patterns and the quantification relationships have not yet been identified. In this study, we focus on the regulatory circuits at the post-transcriptional level, investigating whether and how this principle may apply. RESULTS: By analysing the structure of mrna transcripts in multiple metazoan species, we observed a striking exponential correlation between the length of 3' untranslated regions (3'UTR) and morphological complexity as measured by the number of cell types in each organism. Cellular diversity was similarly associated with the accumulation of microrna genes and their putative targets. We propose that the lengthening of 3'UTRs together with a commensurate exponential expansion in post-transcriptional regulatory circuits can contribute to the emergence of new cell types during animal evolution.
rna polymerase (Pol) III is highly specialized for the production of short non-coding rnas. Once considered to be under relatively simple controls, recent studies using chromatin immunoprecipitation followed by sequen...
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rna polymerase (Pol) III is highly specialized for the production of short non-coding rnas. Once considered to be under relatively simple controls, recent studies using chromatin immunoprecipitation followed by sequencing (ChIP-seq) have revealed unexpected levels of complexity for Pol III regulation, including substantial cell-type selectivity and intriguing overlap with Pol II transcription. Here I describe these novel insights and consider their implications and the questions that remain.
The non-coding rna (ncrna) elements in the 3′ Untranslated Regions (3′-UTRs) are known to participate in the genes' post-transcriptional regulations. Inferring co-expression patterns of the genes through cluster...
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The non-coding rna (ncrna) elements in the 3′ Untranslated Regions (3′-UTRs) are known to participate in the genes' post-transcriptional regulations. Inferring co-expression patterns of the genes through clustering these 3′-UTR ncrna elements will provide invaluable insights for studying their biological functions. In this paper, we propose an improved rna structural clustering pipeline. Benchmark of the new pipeline on Rfam data demonstrates over 10% performance improvements compared to the traditional hierarchical clustering pipeline. By applying the new clustering pipeline to 3′-UTRs of Drosophila melanogaster's genome, we have successfully identified 184 ncrna clusters with 91.3% accuracy. One of these clusters corresponds to genes that are preferentially expressed in male Drosophila. Another cluster contains genes that are responsible for the functions of septate junction in epithelial cells. These discoveries encourage more studies on novel post-transcriptional regulation mechanisms.
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