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Global regulators orchestrate group II intron retromobility.

Colin J Coros1, Carol Lyn Piazza, Venkata R Chalamcharla

  • 1Wadsworth Center, New York State Department of Health, Center for Medical Sciences, 150 New Scotland Avenue, Albany, NY 12208, USA.

Molecular Cell
|April 28, 2009
PubMed
Summary
This summary is machine-generated.

Group II introns, mobile genetic elements, are mobilized by cellular stress molecules cyclic AMP (cAMP) and guanosine tetraphosphate (ppGpp). Metabolic stress activates these molecules, promoting intron movement and genetic diversity.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Microbiology

Background:

  • Group II introns are mobile retroelements with potential links to spliceosomal introns and retrotransposons.
  • These introns move via an RNA intermediate and are found across diverse genomes.
  • Their mobility is crucial for genetic diversity and evolution.

Purpose of the Study:

  • To investigate the role of cellular metabolic regulators in controlling group II intron mobility.
  • To determine if cyclic AMP (cAMP) and guanosine tetraphosphate (ppGpp) influence group II intron retromobility.
  • To elucidate the mechanism by which metabolic stress impacts intron retrotransposition.

Main Methods:

  • Utilized Escherichia coli gene disruption to study enzymes involved in cAMP and ppGpp synthesis.
  • Manipulated cellular conditions (glucose depletion, cAMP supplementation, amino acid starvation) to alter ppGpp levels.
  • Quantified group II intron retromobility, distinguishing between retrotransposition and retrohoming.

Main Results:

  • Disruption of cAMP and ppGpp synthesis pathways inhibited group II intron retromobility.
  • Glucose depletion and cAMP supplementation stimulated intron retromobility in wild-type and mutant cells, respectively.
  • Amino acid starvation, inducing ppGpp, also activated retromobility, favoring retrotransposition over retrohoming.
  • These effects were mediated at the DNA target level, not by altering retroelement expression.

Conclusions:

  • Cellular metabolic state, signaled by cAMP and ppGpp, directly regulates group II intron mobility.
  • Metabolic stress conditions promote group II intron movement, particularly retrotransposition.
  • Group II introns integrate their mobility with global cellular circuitry, contributing to genetic diversity during stress.