The Experts below are selected from a list of 243603 Experts worldwide ranked by ideXlab platform
Dorthe Helena Larsen - One of the best experts on this subject based on the ideXlab platform.
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the nbs1 treacle complex controls ribosomal RNA Transcription in response to dna damage
Nature Cell Biology, 2014Co-Authors: Dorthe Helena Larsen, Flurina J Hari, Julie A Clapperton, Myriam Gwerder, Katrin Gutsche, Matthias Altmeyer, Stephanie Jungmichel, Luis I Toledo, Daniel FinkAbstract:DNA damage induces silencing of ribosomal RNA (rRNA) Transcription. Stucki and colleagues reveal that rRNA silencing is an ATM-dependent pan-nuclear response to irradiation, in which the nucleolar protein Treacle targets DNA-damage protein NBS1 to nucleoli.
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the nbs1 treacle complex controls ribosomal RNA Transcription in response to dna damage
Nature Cell Biology, 2014Co-Authors: Dorthe Helena Larsen, Flurina J Hari, Julie A Clapperton, Myriam Gwerder, Katrin Gutsche, Matthias Altmeyer, Stephanie Jungmichel, Luis I Toledo, Daniel Fink, Majbritt RaskAbstract:Chromosome breakage elicits transient silencing of ribosomal RNA synthesis, but the mechanisms involved remained elusive. Here we discover an in trans signalling mechanism that triggers pan-nuclear silencing of rRNA Transcription in response to DNA damage. This is associated with transient recruitment of the Nijmegen breakage syndrome protein 1 (NBS1), a central regulator of DNA damage responses, into the nucleoli. We further identify TCOF1 (also known as Treacle), a nucleolar factor implicated in ribosome biogenesis and mutated in Treacher Collins syndrome, as an interaction partner of NBS1, and demonstrate that NBS1 translocation and accumulation in the nucleoli is Treacle dependent. Finally, we provide evidence that Treacle-mediated NBS1 recruitment into the nucleoli regulates rRNA silencing in trans in the presence of distant chromosome breaks.
Deedra Nicolet - One of the best experts on this subject based on the ideXlab platform.
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the long non coding RNA hoxb as3 regulates ribosomal RNA Transcription in npm1 mutated acute myeloid leukemia
Nature Communications, 2019Co-Authors: Dimitrios Papaioannou, Andreas Petri, Oliver M Dovey, Sara Terreri, Eric Wang, Frances A Collins, Lauren A Woodward, Allison E Walker, Deedra NicoletAbstract:Long non-coding RNAs (lncRNAs) are important regulatory molecules that are implicated in cellular physiology and pathology. In this work, we dissect the functional role of the HOXB-AS3 lncRNA in patients with NPM1-mutated (NPM1mut) acute myeloid leukemia (AML). We show that HOXB-AS3 regulates the proliferative capacity of NPM1mut AML blasts in vitro and in vivo. HOXB-AS3 is shown to interact with the ErbB3-binding protein 1 (EBP1) and guide EBP1 to the ribosomal DNA locus. Via this mechanism, HOXB-AS3 regulates ribosomal RNA Transcription and de novo protein synthesis. We propose that in the context of NPM1 mutations, HOXB-AS3 overexpression acts as a compensatory mechanism, which allows adequate protein production in leukemic blasts.
Julius B Lucks - One of the best experts on this subject based on the ideXlab platform.
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achieving large dynamic range control of gene expression with a compact RNA Transcription translation regulator
Nucleic Acids Research, 2017Co-Authors: Alexandra Westbrook, Julius B LucksAbstract:RNA Transcriptional regulators are emerging as versatile components for genetic network construction. However, these regulators suffer from incomplete repression in their OFF state, making their dynamic range less than that of their protein counterparts. This incomplete repression causes expression leak, which impedes the construction of larger synthetic regulatory networks as leak propagation can interfere with desired network function. To address this, we demonstrate how naturally derived antisense RNA-mediated Transcriptional regulators can be configured to regulate both Transcription and translation in a single compact RNA mechanism that functions in Escherichia coli. Using in vivo gene expression assays, we show that a combination of Transcriptional termination and ribosome binding site sequestration increases repression from 85% to 98%, or activation from 10-fold to over 900-fold, in response to cognate antisense RNAs. We also show that orthogonal repressive versions of this mechanism can be created through engineering minimal antisense RNAs. Finally, to demonstrate the utility of this mechanism, we use it to reduce network leak in an RNA-only cascade. We anticipate these regulators will find broad use as synthetic biology moves beyond parts engineering to the design and construction of more sophisticated regulatory networks.
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achieving large dynamic range control of gene expression with a compact RNA Transcription translation regulator
bioRxiv, 2016Co-Authors: Alexandra Westbrook, Julius B LucksAbstract:RNA Transcriptional regulators are emerging as versatile components for genetic circuit construction. However, RNA Transcriptional regulators suffer from incomplete repression, making their dynamic range less than that of their protein counterparts. This incomplete repression can cause expression leak, which impedes the construction of larger RNA synthetic regulatory networks. Here we demonstrate how naturally derived antisense RNA-mediated Transcriptional regulators can be configured to regulate both Transcription and translation in a single compact RNA mechanism that functions in Escherichia coli. Using in vivo gene expression assays, we show that a combination of Transcriptional termination and RBS sequestration increases repression from 85% to 98% and activation from 10 fold to over 900 fold in response to cognate antisense RNAs. We also show that orthogonal versions of this mechanism can be created through engineering minimal antisense RNAs. Finally, to demonstrate the utility of this dual control mechanism, we use it to reduce circuit leak in an RNA-only Transcriptional cascade that activates gene expression as a function of a small molecule input. We anticipate these regulators will find broad use as synthetic biology moves beyond parts engineering to the design and construction of larger and more sophisticated circuits.
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a modular strategy for engineering orthogonal chimeric RNA Transcription regulators
Nucleic Acids Research, 2013Co-Authors: M Takahashi, Julius B LucksAbstract:Antisense RNA Transcription attenuators are a key component of the synthetic biology toolbox, with their ability to serve as building blocks for both signal integration logic circuits and Transcriptional cascades. However, a central challenge to building more sophisticated RNA genetic circuitry is creating larger families of orthogonal attenuators that function independently of each other. Here, we overcome this challenge by developing a modular strategy to create chimeric fusions between the engineered Transcriptional attenuator from plasmid pT181 and natural antisense RNA translational regulators. Using in vivo gene expression assays in Escherichia coli, we demonstrate our ability to create chimeric attenuators by fusing sequences from five different translational regulators. Mutagenesis of these functional attenuators allowed us to create a total of 11 new chimeric attenutaors. A comprehensive orthogonality test of these culminated in a 7 × 7 matrix of mutually orthogonal regulators. A comparison between all chimeras tested led to design principles that will facilitate further engineering of orthogonal RNA Transcription regulators, and may help elucidate general principles of non-coding RNA regulation. We anticipate that our strategy will accelerate the development of even larger families of orthogonal RNA Transcription regulators, and thus create breakthroughs in our ability to construct increasingly sophisticated RNA genetic circuitry.
Daniel Fink - One of the best experts on this subject based on the ideXlab platform.
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the nbs1 treacle complex controls ribosomal RNA Transcription in response to dna damage
Nature Cell Biology, 2014Co-Authors: Dorthe Helena Larsen, Flurina J Hari, Julie A Clapperton, Myriam Gwerder, Katrin Gutsche, Matthias Altmeyer, Stephanie Jungmichel, Luis I Toledo, Daniel FinkAbstract:DNA damage induces silencing of ribosomal RNA (rRNA) Transcription. Stucki and colleagues reveal that rRNA silencing is an ATM-dependent pan-nuclear response to irradiation, in which the nucleolar protein Treacle targets DNA-damage protein NBS1 to nucleoli.
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the nbs1 treacle complex controls ribosomal RNA Transcription in response to dna damage
Nature Cell Biology, 2014Co-Authors: Dorthe Helena Larsen, Flurina J Hari, Julie A Clapperton, Myriam Gwerder, Katrin Gutsche, Matthias Altmeyer, Stephanie Jungmichel, Luis I Toledo, Daniel Fink, Majbritt RaskAbstract:Chromosome breakage elicits transient silencing of ribosomal RNA synthesis, but the mechanisms involved remained elusive. Here we discover an in trans signalling mechanism that triggers pan-nuclear silencing of rRNA Transcription in response to DNA damage. This is associated with transient recruitment of the Nijmegen breakage syndrome protein 1 (NBS1), a central regulator of DNA damage responses, into the nucleoli. We further identify TCOF1 (also known as Treacle), a nucleolar factor implicated in ribosome biogenesis and mutated in Treacher Collins syndrome, as an interaction partner of NBS1, and demonstrate that NBS1 translocation and accumulation in the nucleoli is Treacle dependent. Finally, we provide evidence that Treacle-mediated NBS1 recruitment into the nucleoli regulates rRNA silencing in trans in the presence of distant chromosome breaks.
Majbritt Rask - One of the best experts on this subject based on the ideXlab platform.
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the nbs1 treacle complex controls ribosomal RNA Transcription in response to dna damage
Nature Cell Biology, 2014Co-Authors: Dorthe Helena Larsen, Flurina J Hari, Julie A Clapperton, Myriam Gwerder, Katrin Gutsche, Matthias Altmeyer, Stephanie Jungmichel, Luis I Toledo, Daniel Fink, Majbritt RaskAbstract:Chromosome breakage elicits transient silencing of ribosomal RNA synthesis, but the mechanisms involved remained elusive. Here we discover an in trans signalling mechanism that triggers pan-nuclear silencing of rRNA Transcription in response to DNA damage. This is associated with transient recruitment of the Nijmegen breakage syndrome protein 1 (NBS1), a central regulator of DNA damage responses, into the nucleoli. We further identify TCOF1 (also known as Treacle), a nucleolar factor implicated in ribosome biogenesis and mutated in Treacher Collins syndrome, as an interaction partner of NBS1, and demonstrate that NBS1 translocation and accumulation in the nucleoli is Treacle dependent. Finally, we provide evidence that Treacle-mediated NBS1 recruitment into the nucleoli regulates rRNA silencing in trans in the presence of distant chromosome breaks.
