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      Non-coding RNA and its potential role in Mycobacterium tuberculosis pathogenesis

      review-article
      * ,
      RNA Biology
      Landes Bioscience
      Mycobacterium tuberculosis, non-coding RNA, pathogenesis, persistence

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          Abstract

          It is estimated that one third of the human population is infected with Mycobacterium tuberculosis. Efforts to understand the molecular basis of its gene regulation have been focused on identification of protein encoding genes and regulons implicated in pathogenesis. Recently, a number of studies have described the identification of several non-coding RNAs that are likely to contribute significantly to the regulatory networks responsible for adaptation and virulence in M. tuberculosis. We have reviewed emerging information on the presence and abundance of different types of non-coding RNA in M. tuberculosis and consider their potential contribution to the adaptive responses that underlie disease pathogenesis.

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          Most cited references75

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          Genes required for mycobacterial growth defined by high density mutagenesis.

          Despite over a century of research, tuberculosis remains a leading cause of infectious death worldwide. Faced with increasing rates of drug resistance, the identification of genes that are required for the growth of this organism should provide new targets for the design of antimycobacterial agents. Here, we describe the use of transposon site hybridization (TraSH) to comprehensively identify the genes required by the causative agent, Mycobacterium tuberculosis, for optimal growth. These genes include those that can be assigned to essential pathways as well as many of unknown function. The genes important for the growth of M. tuberculosis are largely conserved in the degenerate genome of the leprosy bacillus, Mycobacterium leprae, indicating that non-essential functions have been selectively lost since this bacterium diverged from other mycobacteria. In contrast, a surprisingly high proportion of these genes lack identifiable orthologues in other bacteria, suggesting that the minimal gene set required for survival varies greatly between organisms with different evolutionary histories.
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            CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA.

            Horizontal gene transfer (HGT) in bacteria and archaea occurs through phage transduction, transformation, or conjugation, and the latter is particularly important for the spread of antibiotic resistance. Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci confer sequence-directed immunity against phages. A clinical isolate of Staphylococcus epidermidis harbors a CRISPR spacer that matches the nickase gene present in nearly all staphylococcal conjugative plasmids. Here we show that CRISPR interference prevents conjugation and plasmid transformation in S. epidermidis. Insertion of a self-splicing intron into nickase blocks interference despite the reconstitution of the target sequence in the spliced mRNA, which indicates that the interference machinery targets DNA directly. We conclude that CRISPR loci counteract multiple routes of HGT and can limit the spread of antibiotic resistance in pathogenic bacteria.
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              Regulatory RNAs in bacteria.

              Bacteria possess numerous and diverse means of gene regulation using RNA molecules, including mRNA leaders that affect expression in cis, small RNAs that bind to proteins or base pair with target RNAs, and CRISPR RNAs that inhibit the uptake of foreign DNA. Although examples of RNA regulators have been known for decades in bacteria, we are only now coming to a full appreciation of their importance and prevalence. Here, we review the known mechanisms and roles of regulatory RNAs, highlight emerging themes, and discuss remaining questions.
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                Author and article information

                Journal
                RNA Biol
                RNA Biol
                RNA
                RNA Biology
                Landes Bioscience
                1547-6286
                1555-8584
                01 April 2012
                01 April 2012
                : 9
                : 4
                : 427-436
                Affiliations
                Division of Mycobacterial Research; MRC National Institute for Medical Research; London, UK
                Author notes
                [* ]Correspondence to: Kristine Arnvig, Email: karnvig@ 123456nimr.mrc.ac.uk
                Article
                2011fRNABIOL0124R1 20105
                10.4161/rna.20105
                3384566
                22546938
                fa6cdbe1-535a-40f6-9b51-a32168eb0133
                Copyright © 2012 Landes Bioscience

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                History
                Categories
                Review

                Molecular biology
                mycobacterium tuberculosis,persistence,non-coding rna,pathogenesis
                Molecular biology
                mycobacterium tuberculosis, persistence, non-coding rna, pathogenesis

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