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  • 2013  (48)
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  • 2013  (48)
  • 1
    Description: On November 28, 2012 lexander (lex) öhm, a bacterial geneticist, died at age 41, only a few months after taking up a position as an assistant professor at the enter for ynthetic icrobiology in arburg, ermany. Earlier in 2012 lex had been diagnosed with an aggressive form of thyroid cancer that left him little time to live his scientific and personal dreams.
    Keywords: Bohm, Alexander ; Deaths ; Biologists;
    ISSN: 0950-382X
    E-ISSN: 1365-2958
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  • 2
    In: EMBO Journal, 03 July 2013, Vol.32(13), pp.1802-1804
    Description: CRISPR systems not only defend bacteria from foreign DNA but also contribute to pathogenicity, by regulating endogenous gene expression to evade host innate immune responses.
    Keywords: Animals–Immunology ; Female–Pathogenicity ; Gammaproteobacteria–Immunology ; Gammaproteobacteria–Immunology ; Immune Evasion–Immunology ; Immunity, Innate–Immunology ; Germany ; Prokaryotes ; Gene Expression ; Eukaryotes ; Bacteria ; Molecular Biology;
    ISSN: 0261-4189
    E-ISSN: 1460-2075
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  • 3
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 10 September 2013, Vol.110(37), pp.E3487-96
    Description: Small RNAs (sRNAs) constitute a large and heterogeneous class of bacterial gene expression regulators. Much like eukaryotic microRNAs, these sRNAs typically target multiple mRNAs through short seed pairing, thereby acting as global posttranscriptional regulators. In some bacteria, evidence for hundreds to possibly more than 1,000 different sRNAs has been obtained by transcriptome sequencing. However, the experimental identification of possible targets and, therefore, their confirmation as functional regulators of gene expression has remained laborious. Here, we present a strategy that integrates phylogenetic information to predict sRNA targets at the genomic scale and reconstructs regulatory networks upon functional enrichment and network analysis (CopraRNA, for Comparative Prediction Algorithm for sRNA Targets). Furthermore, CopraRNA precisely predicts the sRNA domains for target recognition and interaction. When applied to several model sRNAs, CopraRNA revealed additional targets and functions for the sRNAs CyaR, FnrS, RybB, RyhB, SgrS, and Spot42. Moreover, the mRNAs gdhA, lrp, marA, nagZ, ptsI, sdhA, and yobF-cspC were suggested as regulatory hubs targeted by up to seven different sRNAs. The verification of many previously undetected targets by CopraRNA, even for extensively investigated sRNAs, demonstrates its advantages and shows that CopraRNA-based analyses can compete with experimental target prediction approaches. A Web interface allows high-confidence target prediction and efficient classification of bacterial sRNAs.
    Keywords: E. Coli ; RNA–RNA Interaction ; Regulatory RNA ; RNA, Bacterial -- Genetics
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 4
    Language: English
    In: Nucleic acids research, 07 January 2013, Vol.41(1), pp.542-53
    Description: Many microRNAs (miRNAs) are co-regulated during the same physiological process but the underlying cellular logic is often little understood. The conserved, immunomodulatory miRNAs miR-146 and miR-155, for instance, are co-induced in many cell types in response to microbial lipopolysaccharide (LPS) to feedback-repress LPS signalling through Toll-like receptor TLR4. Here, we report that these seemingly co-induced regulatory RNAs dramatically differ in their induction behaviour under various stimuli strengths and act non-redundantly through functional specialization; although miR-146 expression saturates at sub-inflammatory doses of LPS that do not trigger the messengers of inflammation markers, miR-155 remains tightly associated with the pro-inflammatory transcriptional programmes. Consequently, we found that both miRNAs control distinct mRNA target profiles; although miR-146 targets the messengers of LPS signal transduction components and thus downregulates cellular LPS sensitivity, miR-155 targets the mRNAs of genes pervasively involved in pro-inflammatory transcriptional programmes. Thus, miR-155 acts as a broad limiter of pro-inflammatory gene expression once the miR-146 dependent barrier to LPS triggered inflammation has been breached. Importantly, we also report alternative miR-155 activation by the sensing of bacterial peptidoglycan through cytoplasmic NOD-like receptor, NOD2. We predict that dose-dependent responses to environmental stimuli may involve functional specialization of seemingly co-induced miRNAs in other cellular circuitries as well.
    Keywords: Immunity, Innate -- Genetics ; Micrornas -- Metabolism
    ISSN: 03051048
    E-ISSN: 1362-4962
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  • 5
    Language: English
    In: Cell, 11 April 2013, Vol.153(2), pp.426-437
    Description: Glucose homeostasis is strictly controlled in all domains of life. Bacteria that are unable to balance intracellular sugar levels and deal with potentially toxic phosphosugars cease growth and risk being outcompeted. Here, we identify the conserved haloacid dehalogenase (HAD)-like enzyme YigL as the previously hypothesized phosphatase for detoxification of phosphosugars and reveal that its synthesis is activated by an Hfq-dependent small RNA in . We show that the glucose-6-P-responsive small RNA SgrS activates YigL synthesis in a translation-independent fashion by the selective stabilization of a decay intermediate of the dicistronic messenger RNA (mRNA). Intriguingly, the major endoribonuclease RNase E, previously known to function together with small RNAs to degrade mRNA targets, is also essential for this process of mRNA activation. The exploitation of and targeted interference with regular RNA turnover described here may constitute a general route for small RNAs to rapidly activate both coding and noncoding genes. ► The bacterial small RNA SgrS posttranscriptionally activates the synthesis of YigL ► YigL is the previously hypothesized phosphatase that prevents phosphosugar toxicity ► SgrS activates yigL by a translation-independent mRNA-stabilization mechanism ► SgrS stabilizes an intermediate in the yigL mRNA decay pathway YigL, a long-sought bacterial phosphatase, regulates glucose-6-phosphate levels. A small regulatory RNA upregulates YigL synthesis by base pairing with the coding sequence of the preceding gene to interfere with endonucleolytic yigL mRNA decay.
    Keywords: Biology
    ISSN: 0092-8674
    E-ISSN: 1097-4172
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  • 6
    In: EMBO Journal, 13 November 2013, Vol.32(22), pp.2963-2979
    Description: Small RNAs use a diversity of well‐characterized mechanisms to repress mRNAs, but how they activate gene expression at the mRNA level remains not well understood. The predominant activation mechanism of Hfq‐associated small RNAs has been translational control whereby base pairing with the target prevents the formation of an intrinsic inhibitory structure in the mRNA and promotes translation initiation. Here, we report a translation‐independent mechanism whereby the small RNA RydC selectively activates the longer of two isoforms of mRNA (encoding cyclopropane fatty acid synthase) in . Target activation is achieved through seed pairing of the pseudoknot‐exposed, conserved 5′ end of RydC to an upstream region of the mRNA. The seed pairing stabilizes the messenger, likely by interfering directly with RNase E‐mediated decay in the 5′ untranslated region. Intriguingly, this mechanism is generic such that the activation is equally achieved by seed pairing of unrelated small RNAs, suggesting that this mechanism may be utilized in the design of RNA‐controlled synthetic circuits. Physiologically, RydC is the first small RNA known to regulate membrane stability. The small RNA RydC stabilizes target mRNAs in a translation‐independent manner through base pairing to the 5′UTR, blocking RNase E access. Cyclopropane fatty acid synthase is a target for RydC, providing the first link between sRNA regulation and membrane biosynthesis in bacteria.
    Keywords: Fatty Acid Synthesis ; Hfq ; Mrna Activation ; Noncoding Rna ; Small Rna
    ISSN: 0261-4189
    E-ISSN: 1460-2075
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  • 7
    Language: English
    In: Molecular Cell, 10 October 2013, Vol.52(1), pp.4-7
    Description: Three papers in this issue of report on the structure and functional activity of type III CRISPR-Cas effector complexes, revealing novel and conserved features of the ribonucleoprotein particles that underlie prokaryotic genome defense. The new structures suggest that type I and type III complexes follow the same architectural principles and are most likely descendants of a common ancestor, the differences in RNA and protein sequences and structure of individual components notwithstanding.
    Keywords: Biology
    ISSN: 1097-2765
    E-ISSN: 1097-4164
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  • 8
    Language: English
    In: Genes & development, 15 May 2013, Vol.27(10), pp.1073-8
    Description: The abundant RNA-binding proteins CsrA and Hfq each impact bacterial physiology by working in conjunction with small RNAs to control large post-transcriptional regulons. The small RNAs involved were considered mechanistically distinct, regulating mRNAs either directly through Hfq-mediated base-pairing or indirectly by sequestering the global translational repressor CsrA. In this issue of Genes & Development, Jørgensen and colleagues (pp. 1132-1145) blur these distinctions with a dual-mechanism small RNA that acts through both Hfq and CsrA to regulate the formation of bacterial biofilms.
    Keywords: Csra ; Csrb ; Hfq ; Pga ; C-Di-Gmp ; Gene Expression Regulation, Bacterial ; Biofilms -- Growth & Development ; Escherichia Coli -- Genetics ; RNA, Bacterial -- Genetics
    ISSN: 08909369
    E-ISSN: 1549-5477
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  • 9
    Language: English
    In: Current Opinion in Microbiology, April 2013, Vol.16(2), pp.109-111
    Keywords: Biology
    ISSN: 1369-5274
    E-ISSN: 1879-0364
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  • 10
    Language: English
    In: Cold Spring Harbor perspectives in medicine, 01 September 2013, Vol.3(9), pp.a010298
    Description: Pathogenic bacteria possess intricate regulatory networks that temporally control the production of virulence factors, and enable the bacteria to survive and proliferate after host infection. Regulatory RNAs are now recognized as important components of these networks, and their study may not only identify new approaches to combat infectious diseases but also reveal new general control mechanisms involved in bacterial gene expression. In this review, we illustrate the diversity of regulatory RNAs in bacterial pathogens, their mechanism of action, and how they can be integrated into the regulatory circuits that govern virulence-factor production.
    Keywords: Bacteria -- Pathogenicity ; RNA, Bacterial -- Physiology ; RNA, Small Untranslated -- Physiology ; Virulence Factors -- Biosynthesis
    E-ISSN: 2157-1422
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