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Structured mRNAs regulate translation initiation by binding to the platform of the ribosome

Stefano Marzi1, Alexander G Myasnikov, Alexander Serganov

  • 1IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Department of Structural Biology and Genomics, Illkirch, F-67404 France.

Cell
|September 25, 2007
PubMed

Insights

Regulatory elements in messenger RNA (mRNA) can control gene expression by stalling protein synthesis. Cryo-electron microscopy visualized how mRNA structures block and then release from the ribosome to regulate translation.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Genetics

Background:

  • Gene expression is tightly regulated at multiple levels.
  • Translation initiation is a key control point for gene expression.
  • Regulatory elements within the 5' untranslated region (5' UTR) of messenger RNAs (mRNAs) can influence translation initiation.

Purpose of the Study:

  • To visualize the structural mechanisms by which 5' UTR mRNA elements regulate translation initiation.
  • To understand how repressor proteins interact with mRNA and the ribosome to control translation.
  • To identify potential universal binding sites on the ribosome for regulatory mRNA elements.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) was used to capture snapshots of ribosomal complexes.
  • Ribosomal complexes were visualized in both stalled (repressed) and active (unfolded mRNA) states.
  • Comparative structural and sequence analysis was performed.

Main Results:

  • Cryo-EM revealed how folded mRNA structures, bound by repressor protein S15, block the ribosome by preventing the start codon from accessing the P-site.
  • Upon repressor release, the mRNA unfolds and enters the ribosomal mRNA channel, allowing translation initiation.
  • A conserved '30S platform' on the ribosome is proposed as a universal site for binding regulatory 5' mRNA elements.

Conclusions:

  • Regulatory 5' UTR mRNA structures can transiently stall ribosomes, providing a mechanism for gene expression control.
  • The ribosome possesses a dedicated platform for accommodating and regulating these mRNA structures during translation preinitiation.
  • This mechanism highlights a conserved strategy for post-transcriptional gene regulation.

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