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Matthias Selbach - One of the best experts on this subject based on the ideXlab platform.

  • mrnas proteins and the emerging principles of Gene Expression Control
    Nature Reviews Genetics, 2020
    Co-Authors: Christopher Buccitelli, Matthias Selbach
    Abstract:

    Gene Expression involves transcription, translation and the turnover of mRNAs and proteins. The degree to which protein abundances scale with mRNA levels and the implications in cases where this dependency breaks down remain an intensely debated topic. Here we review recent mRNA-protein correlation studies in the light of the quantitative parameters of the Gene Expression pathway, contextual confounders and buffering mechanisms. Although protein and mRNA levels typically show reasonable correlation, we describe how transcriptomics and proteomics provide useful non-redundant readouts. Integrating both types of data can reveal exciting biology and is an essential step in refining our understanding of the principles of Gene Expression Control.

  • orchestrated intron retention regulates normal granulocyte differentiation
    Cell, 2013
    Co-Authors: Justin J.-l. Wong, Dadi Gao, William Ritchie, Olivia A Ebner, Matthias Selbach, Jason W H Wong, Yizhou Huang
    Abstract:

    Intron retention (IR) is widely recognized as a consequence of mis-splicing that leads to failed excision of intronic sequences from pre-messenger RNAs. Our bioinformatic analyses of transcriptomic and proteomic data of normal white blood cell differentiation reveal IR as a physiological mechanism of Gene Expression Control. IR regulates the Expression of 86 functionally related Genes, including those that determine the nuclear shape that is unique to granulocytes. Retention of introns in specific Genes is associated with downregulation of splicing factors and higher GC content. IR, conserved between human and mouse, led to reduced mRNA and protein levels by triggering the nonsense-mediated decay (NMD) pathway. In contrast to the prevalent view that NMD is limited to mRNAs encoding aberrant proteins, our data establish that IR coupled with NMD is a conserved mechanism in normal granulopoiesis. Physiological IR may provide an energetically favorable level of dynamic Gene Expression Control prior to sustained Gene translation.

  • corrigendum global quantification of mammalian Gene Expression Control
    Nature, 2013
    Co-Authors: Bjorn Schwanhausser, Dorothea Busse, Gunnar Dittmar, Johannes Schuchhardt, Jana Wolf, Wei Chen, Matthias Selbach
    Abstract:

    Nature 473, 337–342 (2011); doi:10.1038/nature10098 Mark Biggin of the Lawrence Berkeley National Laboratory contacted us, noting that our mass-spectrometry-based protein copy number estimates are lower than several literature-based values. We therefore re-analysed the scripts used for data processing, and found a scaling error that occurred during the conversion of normalized protein intensity values into absolute copy number estimates.

  • global quantification of mammalian Gene Expression Control
    Nature, 2011
    Co-Authors: Bjorn Schwanhausser, Dorothea Busse, Gunnar Dittmar, Johannes Schuchhardt, Jana Wolf, Wei Chen, Matthias Selbach
    Abstract:

    Gene Expression is a multistep process that involves the transcription, translation and turnover of messenger RNAs and proteins. Although it is one of the most fundamental processes of life, the entire cascade has never been quantified on a genome-wide scale. Here we simultaneously measured absolute mRNA and protein abundance and turnover by parallel metabolic pulse labelling for more than 5,000 Genes in mammalian cells. Whereas mRNA and protein levels correlated better than previously thought, corresponding half-lives showed no correlation. Using a quantitative model we have obtained the first genome-scale prediction of synthesis rates of mRNAs and proteins. We find that the cellular abundance of proteins is predominantly Controlled at the level of translation. Genes with similar combinations of mRNA and protein stability shared functional properties, indicating that half-lives evolved under energetic and dynamic constraints. Quantitative information about all stages of Gene Expression provides a rich resource and helps to provide a greater understanding of the underlying design principles.

Alexander Serganov - One of the best experts on this subject based on the ideXlab platform.

  • themes and variations in riboswitch structure and function
    Biochimica et Biophysica Acta, 2014
    Co-Authors: Alla Peselis, Alexander Serganov
    Abstract:

    Abstract The complexity of Gene Expression Control by non-coding RNA has been highlighted by the recent progress in the field of riboswitches. Discovered a decade ago, riboswitches represent a diverse group of non-coding mRNA regions that possess a unique ability to directly sense cellular metabolites and modulate Gene Expression through formation of alternative metabolite-free and metabolite-bound conformations. Such protein-free metabolite sensing domains utilize sophisticated three-dimensional folding of RNA molecules to discriminate between a cognate ligand from related compounds so that only the right ligand would trigger a Genetic response. Given the variety of riboswitch ligands ranging from small cations to large coenzymes, riboswitches adopt a great diversity of structures. Although many riboswitches share structural principles to build metabolite-competent folds, form precise ligand-binding pockets, and communicate a ligand-binding event to downstream regulatory regions, virtually all riboswitch classes possess unique features for ligand recognition, even those tuned to recognize the same metabolites. Here we present an overview of the biochemical and structural research on riboswitches with a major focus on common principles and individual characteristics adopted by these regulatory RNA elements during evolution to specifically target small molecules and exert Genetic responses. This article is part of a Special Issue entitled: Riboswitches.

  • structural insights into ligand binding and Gene Expression Control by an adenosylcobalamin riboswitch
    Nature Structural & Molecular Biology, 2012
    Co-Authors: Alla Peselis, Alexander Serganov
    Abstract:

    Adenosylcobalamin is a form of vitamin B12 that serves as a coenzyme in different reactions and as a ligand for riboswitches to Control bacterial Gene Expression. The crystal structure of a B12 riboswitch from Symbiobacterium thermophilum bound to its ligand adenosylcobalamin is now presented, revealing the determinants for ligand recognition and Gene Expression Control.

  • ribozymes riboswitches and beyond regulation of Gene Expression without proteins
    Nature Reviews Genetics, 2007
    Co-Authors: Alexander Serganov, Dinshaw J Patel
    Abstract:

    Recent findings suggest that RNA-based elements such as ribozymes and RNA sensors have a widespread role in Gene Expression regulation. Studies of these RNAs provide insights into mechanisms of Gene Expression Control and the evolution of cellular functions from RNA-based origins.

Justin J.-l. Wong - One of the best experts on this subject based on the ideXlab platform.

  • intron retention enhances Gene regulatory complexity in vertebrates
    Genome Biology, 2017
    Co-Authors: Ulf Schmitz, Justin J.-l. Wong, Natalia Pinello, William Ritchie, Fangzhi Jia, Sultan Alasmari, Maria-cristina Keightley, Shaniko Shini, Graham Lieschke, John E.j. Rasko
    Abstract:

    While intron retention (IR) is now widely accepted as an important mechanism of mammalian Gene Expression Control, it remains the least studied form of alternative splicing. To delineate conserved features of IR, we performed an exhaustive phyloGenetic analysis in a highly purified and functionally defined cell type comprising neutrophilic granulocytes from five vertebrate species spanning 430 million years of evolution. Our RNA-sequencing-based analysis suggests that IR increases Gene regulatory complexity, which is indicated by a strong anti-correlation between the number of Genes affected by IR and the number of protein-coding Genes in the genome of individual species. Our results confirm that IR affects many orthologous or functionally related Genes in granulocytes. Further analysis uncovers new and unanticipated conserved characteristics of intron-retaining transcripts. We find that intron-retaining Genes are transcriptionally co-regulated from bidirectional promoters. Intron-retaining Genes have significantly longer 3′ UTR sequences, with a corresponding increase in microRNA binding sites, some of which include highly conserved sequence motifs. This suggests that intron-retaining Genes are highly regulated post-transcriptionally. Our study provides unique insights concerning the role of IR as a robust and evolutionarily conserved mechanism of Gene Expression regulation. Our findings enhance our understanding of Gene regulatory complexity by adding another contributor to evolutionary adaptation.

  • Intron retention is regulated by altered MeCP2-mediated splicing factor recruitment
    Nature Communications, 2017
    Co-Authors: Justin J.-l. Wong, Rajini Nagarajah, Dadi Gao, Trung V. Nguyen, Chau-to Kwok, Michelle Van Geldermalsen, Rob Middleton, Natalia Pinello, Annora Thoeng, Jeff Holst
    Abstract:

    Intron retention is a conserved mechanism that Controls Gene Expression but its regulation is poorly understood. Here, the authors provide evidence that DNA methylation regulates intron retention and find reduced MeCP2 occupancy and splicing factor recruitment near affected splice junctions. While intron retention (IR) is considered a widely conserved and distinct mechanism of Gene Expression Control, its regulation is poorly understood. Here we show that DNA methylation directly regulates IR. We also find reduced occupancy of MeCP2 near the splice junctions of retained introns, mirroring the reduced DNA methylation at these sites. Accordingly, MeCP2 depletion in tissues and cells enhances IR. By analysing the MeCP2 interactome using mass spectrometry and RNA co-precipitation, we demonstrate that decreased MeCP2 binding near splice junctions facilitates IR via reduced recruitment of splicing factors, including Tra2b, and increased RNA polymerase II stalling. These results suggest an association between IR and a slower rate of transcription elongation, which reflects inefficient splicing factor recruitment. In summary, our results reinforce the interdependency between alternative splicing involving IR and epiGenetic Controls of Gene Expression.

  • orchestrated intron retention regulates normal granulocyte differentiation
    Cell, 2013
    Co-Authors: Justin J.-l. Wong, Dadi Gao, William Ritchie, Olivia A Ebner, Matthias Selbach, Jason W H Wong, Yizhou Huang
    Abstract:

    Intron retention (IR) is widely recognized as a consequence of mis-splicing that leads to failed excision of intronic sequences from pre-messenger RNAs. Our bioinformatic analyses of transcriptomic and proteomic data of normal white blood cell differentiation reveal IR as a physiological mechanism of Gene Expression Control. IR regulates the Expression of 86 functionally related Genes, including those that determine the nuclear shape that is unique to granulocytes. Retention of introns in specific Genes is associated with downregulation of splicing factors and higher GC content. IR, conserved between human and mouse, led to reduced mRNA and protein levels by triggering the nonsense-mediated decay (NMD) pathway. In contrast to the prevalent view that NMD is limited to mRNAs encoding aberrant proteins, our data establish that IR coupled with NMD is a conserved mechanism in normal granulopoiesis. Physiological IR may provide an energetically favorable level of dynamic Gene Expression Control prior to sustained Gene translation.

Mohammad Ehsan Bin Mansoor - One of the best experts on this subject based on the ideXlab platform.

  • an expanded synthetic biology toolkit for Gene Expression Control in acetobacteraceae
    ACS Synthetic Biology, 2019
    Co-Authors: Mohammad Ehsan Bin Mansoor
    Abstract:

    The availability of different host chassis will greatly expand the range of applications in synthetic biology. Members of the Acetobacteraceae family of Gram-negative bacteria form an attractive class of nonmodel microorganisms that can be exploited to produce industrial chemicals, food and beverage, and biomaterials. One such biomaterial is bacterial cellulose, which is a strong and ultrapure natural polymer used in tissue engineering scaffolds, wound dressings, electronics, food additives, and other products. However, despite the potential of Acetobacteraceae in biotechnology, there has been considerably little effort to fundamentally reprogram the bacteria for enhanced performance. One limiting factor is the lack of a well-characterized, comprehensive toolkit to Control Expression of Genes in biosynthetic pathways and regulatory networks to optimize production and cell viability. Here, we address this shortcoming by building an expanded Genetic toolkit for synthetic biology applications in Acetobactera...

  • An Expanded Synthetic Biology Toolkit for Gene Expression Control in Acetobacteraceae
    2019
    Co-Authors: Min Yan Teh, Mohammad Ehsan Bin Mansoor, Kean Hean Ooi, Shun Xiang Danny Teo, Wen Zheng Shaun Lim, Meng How Tan
    Abstract:

    The availability of different host chassis will greatly expand the range of applications in synthetic biology. Members of the Acetobacteraceae family of Gram-negative bacteria form an attractive class of nonmodel microorganisms that can be exploited to produce industrial chemicals, food and beverage, and biomaterials. One such biomaterial is bacterial cellulose, which is a strong and ultrapure natural polymer used in tissue engineering scaffolds, wound dressings, electronics, food additives, and other products. However, despite the potential of Acetobacteraceae in biotechnology, there has been considerably little effort to fundamentally reprogram the bacteria for enhanced performance. One limiting factor is the lack of a well-characterized, comprehensive toolkit to Control Expression of Genes in biosynthetic pathways and regulatory networks to optimize production and cell viability. Here, we address this shortcoming by building an expanded Genetic toolkit for synthetic biology applications in Acetobacteraceae. We characterized the performance of multiple natural and synthetic promoters, ribosome binding sites, terminators, and degradation tags in three different strains, namely, Gluconacetobacter xylinus ATCC 700178, Gluconacetobacter hansenii ATCC 53582, and Komagataeibacter rhaeticus iGEM. Our quantitative data revealed strain-specific and common design rules for the precise Control of Gene Expression in these industrially relevant bacterial species. We further applied our tools to synthesize a biodegradable cellulose-chitin copolymer, adjust the structure of the cellulose film produced, and implement CRISPR interference for ready down-regulation of Gene Expression. Collectively, our Genetic parts will enable the efficient engineering of Acetobacteraceae bacteria for the biomanufacturing of cellulose-based materials and other commercially valuable products

Sang Yup Lee - One of the best experts on this subject based on the ideXlab platform.

  • genome engineering and Gene Expression Control for bacterial strain development
    Biotechnology Journal, 2015
    Co-Authors: Chan Woo Song, Joungmin Lee, Sang Yup Lee
    Abstract:

    In recent years, a number of techniques and tools have been developed for genome engineering and Gene Expression Control to achieve desired phenotypes of various bacteria. Here we review and discuss the recent advances in bacterial genome manipulation and Gene Expression Control techniques, and their actual uses with accompanying examples. Genome engineering has been commonly performed based on homologous recombination. During such genome manipulation, the counterselection systems employing SacB or nucleases have mainly been used for the efficient selection of desired engineered strains. The recombineering technology enables simple and more rapid manipulation of the bacterial genome. The group II intron-mediated genome engineering technology is another option for some bacteria that are difficult to be engineered by homologous recombination. Due to the increasing demands on high-throughput screening of bacterial strains having the desired phenotypes, several multiplex genome engineering techniques have recently been developed and validated in some bacteria. Another approach to achieve desired bacterial phenotypes is the repression of target Gene Expression without the modification of genome sequences. This can be performed by expressing antisense RNA, small regulatory RNA, or CRISPR RNA to repress target Gene Expression at the transcriptional or translational level. All of these techniques allow efficient and rapid development and screening of bacterial strains having desired phenotypes, and more advanced techniques are expected to be seen.

  • Design and use of synthetic regulatory small RNAs to Control Gene Expression in Escherichia coli
    Nature Protocols, 2013
    Co-Authors: Seung Min Yoo, Sang Yup Lee
    Abstract:

    Gene knockout experiments are often essential in functional genomics and metabolic engineering studies. However, repeated multiple Gene knockout experiments are laborious, time consuming and sometimes impossible to perform for those Genes that are essential for cell function. Small regulatory RNAs (sRNAs) are short noncoding RNAs in prokaryotes that can finely Control the Expression of target Genes in trans at the post-transcriptional level. Here we describe the protocol for synthetic sRNA-based Gene Expression Control, including sRNA design principles. Customized synthetic sRNAs consist of a scaffold and a target-binding sequence, and they can be created by simply replacing an existing target-binding sequence with one that is complementary to the target mRNA to be repressed, while retaining the scaffold. Our plasmid-based synthetic sRNA system does not require chromosomal modifications, and it enables one to perform high-throughput studies on the effects of knockdowns on host cell physiology, and it further allows the simultaneous screening of target Genes in different Escherichia coli strains for applications in metabolic engineering and synthetic biology. Once an sRNA scaffold-harboring plasmid is constructed, customized synthetic sRNAs can be made within 3–4 d; after this time, the synthetic sRNAs can be applied to the desired experiments.