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Programmed drug-dependent ribosome stalling

Haripriya Ramu1, Alexander Mankin, Nora Vazquez-Laslop

  • 1Center for Pharmaceutical Biotechnology, University of Illinois, 900 S. Ashland Ave., Chicago, IL 60607, USA.

Molecular Microbiology
|January 28, 2009
PubMed

Insights

Ribosomes can sense nascent peptide sequence and structure, regulating gene expression. This mechanism, involving programmed ribosome stalling, is key for antibiotic resistance gene activation.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • The ribosome possesses an intrinsic ability to monitor nascent peptide sequence and structure.
  • This capability is crucial for regulating gene expression, particularly for antibiotic resistance.
  • Ribosome-targeting antibiotics often induce resistance genes via programmed stalling.

Purpose of the Study:

  • To review the molecular mechanisms underlying drug- and nascent peptide-dependent ribosome stalling.
  • To elucidate how ribosomes sense and respond to both external (antibiotic) and internal (peptide sequence) cues.

Main Methods:

  • This review synthesizes existing research on ribosome stalling mechanisms.
  • Focuses on the interplay between antibiotics, nascent peptide sequence, and ribosome function.
  • Integrates findings from structural biology, genetics, and biochemical studies.

Main Results:

  • Ribosome stalling is a programmed event occurring at specific regulatory sequences.
  • The presence of antibiotics in the ribosome exit tunnel is a critical factor.
  • The sequence of the nascent peptide itself directly influences stalling.
  • Formation of the stalled translation complex is dependent on both antibiotic presence and peptide sequence.

Conclusions:

  • Ribosome stalling is a sophisticated regulatory mechanism exploited for gene expression control.
  • Understanding these mechanisms is vital for developing new strategies against antibiotic resistance.
  • The ribosome acts as a central sensor integrating antibiotic and peptide information.

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