MECHANISM OF CSRA MEDIATED GLOBAL CONTROL

  • Babitzke, Paul Lee (PI)
  • Romeo, Tony (PI)
  • Romeo, Tony (PI)
  • Romeo, Tony (CoPI)
  • Romeo, Tony (CoPI)
  • Romeo, Tony (CoPI)
  • BABITZKE, PAUL L. (PI)
  • Romeo, Tony (PI)
  • Romeo, Tony (PI)
  • BABITZKE, PAUL L. (PI)
  • BABITZKE, PAUL L. (PI)
  • Romeo, Tony (PI)

Project: Research project

Project Details

Description

Insight into post-transcriptional regulatory mechanisms of bacterial
gene expression will be sought through the study of a novel paradigm
in global regulation, the carbon storage regulatory system (Csr) of Escherichia
coIi. Csr includes an RNA-binding protein, CsrA, which is a potent modulator of
specific mRNA stability, and a non-coding RNA molecule, CsrB. CsrB forms a
ribonucleoprotein complex with CsrA and antagonizes its activity. It is
hypothesized that CsrB RNA abrogates repression by competing with regulated
mRNAs for binding to CsrA, essentially "titrating-out" the CsrA protein. In E.
coli, CsrA affects metabolism, physiology and cell surface properties on a
broad scale, repressing certain genes expressed during the transition from the
exponential phase of growth into stationary phase and activating various genes
expressed in the exponential phase. Homologs of csrA are widely-distributed
among eubacteria and repress the expression of virulence factors in both plant
and animal pathogens. Thus, the proposed studies will also provide fundamental
understanding of the regulation of bacterial physiology and pathogenesis, and
may suggest novel therapeutic approaches for bacterial infections.

Specific aims of this proposal are: 1) To further define the molecular
mechanism by which CsrA facilitates mRNA decay. This will include determination
of the sequence and structural requirements for mRNA recognition, and the
Potential regulatory role(s) of CsrA in translational inhibition and/or in the
facilitation of endonucleolytic cleavage of target transcripts. 2) We will
assess the molecular mechanism and regulatory role of CsrB in antagonizing the
activity of CsrA. The effects of CsrB on CsrA-regulated mRNA decay will be
determined in vivo, and the isolated CsrA-CsrB complex will be characterized to
determine the CsrB RNA segments involved in CsrA binding. 3) The means by which
the Csr system mediates response to environmental and physiological conditions
will be explored by determining the genetic, physiological and temporal factors
which influence CsrA and CsrB levels and csrA and csrB gene expression. The
long-range basic objectives of our investigations in this area are to fully
understand the regulatory components and genetic circuitry, molecular
mechanisms, and regulatory/biological functions of the Csr system.
StatusActive
Effective start/end date8/1/995/31/21

Funding

  • National Institute of General Medical Sciences: $392,077.00
  • National Institute of General Medical Sciences: $403,014.00
  • National Institute of General Medical Sciences: $425,851.00
  • National Institute of General Medical Sciences: $438,976.00
  • National Institute of General Medical Sciences: $395,964.00
  • National Institute of General Medical Sciences: $425,851.00
  • National Institute of General Medical Sciences: $403,014.00
  • National Institute of General Medical Sciences: $413,901.00
  • National Institute of General Medical Sciences: $196,520.00
  • National Institute of General Medical Sciences: $184,064.00
  • National Institute of General Medical Sciences: $394,789.00
  • National Institute of General Medical Sciences: $402,900.00
  • National Institute of General Medical Sciences: $399,963.00

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