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Ribosome regulation by the nascent peptide

P S Lovett1, E J Rogers

  • 1Department of Biological Sciences, University of Maryland, Catonsville 21228, USA. lovett@umbc.edu

Microbiological Reviews
|June 1, 1996
PubMed
Summary
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Short peptides encoded by upstream genes act as negative regulators of translation. These peptides, called leader peptides or upstream open reading frames (uORFs), stall ribosomes, controlling gene expression in bacteria and eukaryotes.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Bacterial and eukaryotic systems utilize two-gene operons where upstream gene products regulate downstream gene translation.
  • Upstream gene products, termed leader peptides or upstream open reading frames (uORFs), encode short peptides that inhibit ribosome function.
  • These peptides act as cis-acting negative regulators, influencing translation before ribosomal emergence.

Purpose of the Study:

  • To investigate the mechanism of cis-acting translational regulation by leader peptides and uORFs.
  • To elucidate the role of these peptides in biological processes like translation attenuation.
  • To explore the biochemical basis for how nascent peptides modulate ribosome activity.

Main Methods:

  • Genetic studies to identify the role of nascent peptides in ribosome stalling.

Related Experiment Videos

  • In vitro biochemical assays using synthetic leader peptides to assess ribosomal peptidyltransferase inhibition.
  • Analysis of rRNA-binding properties of leader peptides.

    • Main Results:

    • Leader peptides and uORFs regulate translation by interfering with ribosome function.
    • Translation attenuation of bacterial chloramphenicol resistance genes (cat and cmlA) involves ribosome stalling mediated by leader peptides.
    • In vitro studies show leader peptides inhibit ribosomal peptidyltransferase and bind to 23S rRNA at the peptidyl transferase center.

    Conclusions:

    • Nascent peptides encoded by leader regions or uORFs are key regulators of gene expression.
    • These peptides can directly inhibit ribosome activity, potentially through interactions with rRNA.
    • This mechanism provides a gene-specific control of translation in both prokaryotic and eukaryotic systems.