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  • Gene Expression Regulation, Bacterial  (10)
  • Hfq
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  • 1
    Language: English
    In: Molecular Cell, 04 February 2016, Vol.61(3), pp.352-363
    Description: Small RNAs (sRNAs) from conserved noncoding genes are crucial regulators in bacterial signaling pathways but have remained elusive in the Cpx response to inner membrane stress. Here we report that an alternative biogenesis pathway releasing the conserved mRNA 3′ UTR of stress chaperone CpxP as an ∼60-nt sRNA provides the noncoding arm of the Cpx response. This so-called CpxQ sRNA, generated by general mRNA decay through RNase E, acts as an Hfq-dependent repressor of multiple mRNAs encoding extracytoplasmic proteins. Both CpxQ and the Cpx pathway are required for cell survival under conditions of dissipation of membrane potential. Our discovery of CpxQ illustrates how the conversion of a transcribed 3′ UTR into an sRNA doubles the output of a single mRNA to produce two factors with spatially segregated functions during inner membrane stress: a chaperone that targets problematic proteins in the periplasm and a regulatory RNA that dampens their synthesis in the cytosol. Chao and Vogel discover that a small RNA cleaved off the 3′ end of an mRNA provides the elusive regulatory noncoding arm of the bacterial Cpx response to inner membrane stress.
    Keywords: Cpx Pathway ; Cpxp ; Cpxq ; 3′ Utr ; Hfq ; Rnase E ; Noncoding RNA ; Nhab ; Envelope Stress ; Membrane Potential ; Biology
    ISSN: 1097-2765
    E-ISSN: 1097-4164
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  • 2
    In: EMBO Journal, 17 October 2012, Vol.31(20), pp.4005-4019
    Description: The small RNAs associated with the protein Hfq constitute one of the largest classes of post‐transcriptional regulators known to date. Most previously investigated members of this class are encoded by conserved free‐standing genes. Here, deep sequencing of Hfq‐bound transcripts from multiple stages of growth of revealed a plethora of new small RNA species from within mRNA loci, including DapZ, which overlaps with the 3′ region of the biosynthetic gene, . Synthesis of the DapZ small RNA is independent of DapB protein synthesis, and is controlled by HilD, the master regulator of invasion genes. DapZ carries a short G/U‐rich domain similar to that of the globally acting GcvB small RNA, and uses GcvB‐like seed pairing to repress translation of the major ABC transporters, DppA and OppA. This exemplifies double functional output from an mRNA locus by the production of both a protein and an Hfq‐dependent ‐acting RNA. Our atlas of Hfq targets suggests that the 3′ regions of mRNA genes constitute a rich reservoir that provides the Hfq network with new regulatory small RNAs. Deep sequencing of Hfq‐binding RNAs isolated from at different growth stages reveals that the 3′ UTR of bacterial mRNAs are a rich source of regulatory small RNAs which modulate gene expression in trans.
    Keywords: Abc Transporter ; Dapz ; Gcvb ; Hfq ; 3′ Utr
    ISSN: 0261-4189
    E-ISSN: 1460-2075
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  • 3
    Language: English
    In: Frontiers in cellular and infection microbiology, 2014, Vol.4, pp.91
    Description: Enteric pathogens often cycle between virulent and saprophytic lifestyles. To endure these frequent changes in nutrient availability and composition bacteria possess an arsenal of regulatory and metabolic genes allowing rapid adaptation and high flexibility. While numerous proteins have been characterized with regard to metabolic control in pathogenic bacteria, small non-coding RNAs have emerged as additional regulators of metabolism. Recent advances in sequencing technology have vastly increased the number of candidate regulatory RNAs and several of them have been found to act at the interface of bacterial metabolism and virulence factor expression. Importantly, studying these riboregulators has not only provided insight into their metabolic control functions but also revealed new mechanisms of post-transcriptional gene control. This review will focus on the recent advances in this area of host-microbe interaction and discuss how regulatory small RNAs may help coordinate metabolism and virulence of enteric pathogens.
    Keywords: Csra ; Hfq ; Carbon Metabolism ; Srna ; Virulence ; Energy Metabolism ; Carbon -- Metabolism ; Intestines -- Microbiology ; RNA, Small Untranslated -- Genetics
    E-ISSN: 2235-2988
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  • 4
    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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  • 5
    Language: English
    In: RNA biology, 2014, Vol.11(5), pp.403-12
    Description: On June 4-8, 2013, the 3rd Conference on Regulation with RNA in Bacteria took place in Würzburg, Germany. Following two earlier meetings in Berlin and San Juan, this conference has established itself as the primary bi-annual meeting for everyone interested in RNA-based regulations in prokaryotes. The 2013 meeting was organized by Joel Belasco, Susan Gottesman, Franz Narberhaus, and Jörg Vogel. Close to 300 participants from more than 27 countries in Europe, North America, and Asia enjoyed four days of talks and posters on many experimental and biocomputational aspects of prokaryotic RNA biology.
    Keywords: Cascade ; Hfq ; RNA Stability ; RNA-Seq Crispr ; Bioinformatics ; Ribonucleoprotein Complex ; Small RNA ; Gene Expression Regulation, Bacterial ; Bacteria -- Genetics ; RNA, Bacterial -- Genetics
    E-ISSN: 1555-8584
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 6
    Language: English
    In: Molecular Cell, 05 January 2017, Vol.65(1), pp.39-51
    Description: Understanding RNA processing and turnover requires knowledge of cleavages by major endoribonucleases within a living cell. We have employed TIER-seq (transiently inactivating an endoribonuclease followed by RNA-seq) to profile cleavage products of the essential endoribonuclease RNase E in . A dominating cleavage signature is the location of a uridine two nucleotides downstream in a single-stranded segment, which we rationalize structurally as a key recognition determinant that may favor RNase E catalysis. Our results suggest a prominent biogenesis pathway for bacterial regulatory small RNAs whereby RNase E acts together with the RNA chaperone Hfq to liberate stable 3′ fragments from various precursor RNAs. Recapitulating this process in vitro, Hfq guides RNase E cleavage of a representative small-RNA precursor for interaction with a mRNA target. In vivo, the processing is required for target regulation. Our findings reveal a general maturation mechanism for a major class of post-transcriptional regulators. Chao et al. discover that the essential bacterial RNase E cleaves numerous transcripts at preferred sites by sensing uridine as a 2-nt ruler. RNase E processing of various precursor RNAs produces many small regulatory RNAs, constituting a major small-RNA biogenesis pathway in bacteria.
    Keywords: Rnase E ; RNA Degradome ; Non-Coding RNA ; Hfq ; 3′ Utr ; Arcz ; Rpra ; Srna Maturation ; Uridine Ruler ; Tier-Seq ; Biology
    ISSN: 1097-2765
    E-ISSN: 1097-4164
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  • 7
    Language: English
    In: Biological chemistry, December 2005, Vol.386(12), pp.1219-38
    Description: Small non-coding RNAs (sRNAs) have attracted considerable attention as an emerging class of gene expression regulators. In bacteria, a few regulatory RNA molecules have long been known, but the extent of their role in the cell was not fully appreciated until the recent discovery of hundreds of potential sRNA genes in the bacterium Escherichia coli. Orthologs of these E. coli sRNA genes, as well as unrelated sRNAs, were also found in other bacteria. Here we review the disparate experimental approaches used over the years to identify sRNA molecules and their genes in prokaryotes. These include genome-wide searches based on the biocomputational prediction of non-coding RNA genes, global detection of non-coding transcripts using microarrays, and shotgun cloning of small RNAs (RNomics). Other sRNAs were found by either co-purification with RNA-binding proteins, such as Hfq or CsrA/RsmA, or classical cloning of abundant small RNAs after size fractionation in polyacrylamide gels. In addition, bacterial genetics offers powerful tools that aid in the search for sRNAs that may play a critical role in the regulatory circuit of interest, for example, the response to stress or the adaptation to a change in nutrient availability. Many of the techniques discussed here have also been successfully applied to the discovery of eukaryotic and archaeal sRNAs.
    Keywords: Gene Expression Regulation, Bacterial ; RNA, Bacterial ; RNA, Untranslated ; RNA-Binding Proteins
    ISSN: 1431-6730
    E-ISSN: 14374315
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  • 8
    Language: English
    In: RNA Biology, 01 July 2009, Vol.6(3), pp.266-275
    Description: The bacterial Sm-like protein, Hfq, is a key factor for the stability and function of small noncoding RNAs (sRNAs) in E. coli. Homologues of this protein have been predicted in many distantly related organisms yet their functional conservation as sRNA-binding proteins has not entirely been...
    Keywords: Anatomy & Physiology
    ISSN: 1547-6286
    E-ISSN: 1555-8584
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  • 9
    In: mBio, 2019, Vol.10(1)
    Description: The protein ProQ has recently been discovered as the centerpiece of a previously overlooked “third domain” of small RNA-mediated control of gene expression in bacteria. As in vitro work continues to reveal molecular mechanisms, it is also important to understand how ProQ affects the life cycle of bacterial pathogens as these pathogens infect eukaryotic cells. Here, we have determined how ProQ shapes Salmonella virulence and how the activities of this RNA-binding protein compare with those of Hfq, another central protein in RNA-based gene regulation in this and other bacteria. To this end, we apply global transcriptomics of pathogen and host cells during infection. In doing so, we reveal ProQ-dependent transcript changes in key virulence and host immune pathways. Moreover, we differentiate the roles of ProQ from those of Hfq during infection, for both coding and noncoding transcripts, and provide an important resource for those interested in ProQ-dependent small RNAs in enteric bacteria. ABSTRACT FinO domain proteins such as ProQ of the model pathogen Salmonella enterica have emerged as a new class of major RNA-binding proteins in bacteria. ProQ has been shown to target hundreds of transcripts, including mRNAs from many virulence regions, but its role, if any, in bacterial pathogenesis has not been studied. Here, using a Dual RNA-seq approach to profile ProQ-dependent gene expression changes as Salmonella infects human cells, we reveal dysregulation of bacterial motility, chemotaxis, and virulence genes which is accompanied by altered MAPK (mitogen-activated protein kinase) signaling in the host. Comparison with the other major RNA chaperone in Salmonella , Hfq, reinforces the notion that these two global RNA-binding proteins work in parallel to ensure full virulence. Of newly discovered infection-associated ProQ-bound small noncoding RNAs (sRNAs), we show that the 3′UTR-derived sRNA STnc540 is capable of repressing an infection-induced magnesium transporter mRNA in a ProQ-dependent manner. Together, this comprehensive study uncovers the relevance of ProQ for Salmonella pathogenesis and highlights the importance of RNA-binding proteins in regulating bacterial virulence programs.
    Keywords: Research Article ; Molecular Biology And Physiology ; Editor'S Pick ; Hfq ; Noncoding Rna ; Proq ; Rna-Seq ; Bacterial Pathogen ; Posttranscriptional Control
    ISSN: 21612129
    E-ISSN: 2150-7511
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  • 10
    Language: English
    In: Genes & Development, 2005, Vol.19(19), pp.2355-2366
    Description: This paper shows that the small RNA MicA (previously SraD) is an antisense regulator of ompA in Escherichia coli. MicA accumulates upon entry into stationary phase and down-regulates the level of ompA mRNA. Regulation of ompA (outer membrane protein A), previously attributed to Hfq/mRNA binding, is lost...
    Keywords: Medical And Health Sciences ; Medicin Och Hälsovetenskap ; Antisense Rna ; Hfq ; Ompa ; Regulatory Rna ; Translational Control
    ISSN: 0890-9369
    E-ISSN: 15495477
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