Abdalla Al Refaii

Paris Diderot University, Lutetia Parisorum, Île-de-France, France

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Publications (3)10.05 Total impact

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    ABSTRACT: E. coli NusA and NusB proteins bind specific sites, such as those in the leader and spacer sequences that flank the 16S region of the ribosomal RNA transcript, forming a complex with RNA polymerase that suppresses Rho-dependent transcription termination. Although antitermination has long been the accepted role for Nus factors in rRNA synthesis, we propose that another major role for the Nus modified transcription complex in rrn operons is as an RNA chaperone insuring coordination of 16S rRNA folding and RNase III processing that results in production of proper 30S ribosome subunits. This contrarian proposal is based on our studies of nusA and nusB cold-sensitive mutations that have altered translation and at low temperature accumulate 30S subunit precursors. Both phenotypes are suppressed by deletion of RNase III. We argue that these results are consistent with the idea that the nus mutations cause altered rRNA folding that leads to abnormal 30S subunits and slow translation. According to this idea, functional Nus proteins stabilize an RNA loop between their binding sites in the 5' RNA leader and on the transcribing RNA polymerase, providing a topological constraint on the RNA that aids normal rRNA folding and processing.
    Molecular Microbiology 11/2012; · 5.03 Impact Factor
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    Abdalla Al Refaii, Jean-Hervé Alix
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    ABSTRACT: In Escherichia coli strains carrying null mutations in either the dnaK or dnaJ genes, the late stages of 30S and 50S ribosomal subunit biogenesis are slowed down in a temperature-dependent manner. At high temperature (44 degrees C), 32S and 45S particles (precursors to 50S subunits) and 21S particles (precursors to 30S subunits) accumulate. The latter are shown by 3'5' rapid amplification of cDNA ends analysis to contain unprocessed or partially processed 16S ribosomal RNA at the 5' end, but the 3' end was never processed. This implies that maturation of 16S ribosomal RNA starts at the 5'-terminus, and that the 3'-terminus is only trimmed at a later step. At normal temperatures (30 degrees C-37 degrees C), ribosome assembly in both mutants is not arrested but is significantly delayed, as shown by pulse-chase analysis. Assembly defects are partially compensated by an overexpression of other heat-shock proteins, which occurs in the absence of their negative regulator DnaK, or by a plasmid-driven overexpression of GroES/GroEL, suggesting the involvement of a network of chaperones in ribosome biogenesis.
    Molecular Microbiology 01/2009; 71(3):748-62. · 5.03 Impact Factor
  • Abdalla Al Refaii, Jean-Hervé Alix
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    ABSTRACT: In Escherichia coli, the molecular chaperone HSP70 (DnaK) is necessary for 30S and 50S ribosomal subunit assembly at temperatures above 37 degrees C. Inhibitors of DnaK should therefore hinder ribosome biogenesis, in addition to all of the other DnaK-dependent cellular functions. An easily testable phenotype of DnaK is described here based on alpha-complementation of beta-galactosidase. This protein fragment complementation requires a functional DnaK in vivo, offering a suitable method for screening for DnaK inhibitors. Subsequently, it will be of great importance to check whether inhibitors of bacterial DnaK selected in this way have an effect (inhibitory or stimulatory) on the activities of eukaryotic HSP70 and HSC70 chaperones, because of the universal conservation in all biota of these chaperones in both their structural and functional properties. This question is important due to their implication in many pathways in immunology, cancer biology, and neurodegenerative disorders.
    Methods in molecular medicine 02/2008; 142:75-85.

Publication Stats

29 Citations
10.05 Total Impact Points

Institutions

  • 2012
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
    • National Cancer Institute (USA)
      Maryland, United States
  • 2009
    • Pierre and Marie Curie University - Paris 6
      • Institut de Biologie Physico-Chimique (IBPC) (CNRS)
      Lutetia Parisorum, Île-de-France, France
  • 2008
    • French National Centre for Scientific Research
      • Institut de Biologie Physico-Chimique
      Paris, Ile-de-France, France