Ribosome profiling reveals sequence-independent post-initiation pausing as a signature of translation

Cell Res. 2014 Jul;24(7):842-51. doi: 10.1038/cr.2014.74. Epub 2014 Jun 6.

Abstract

The journey of a newly synthesized polypeptide starts in the peptidyltransferase center of the ribosome, from where it traverses the exit tunnel. The interior of the ribosome exit tunnel is neither straight nor smooth. How the ribosome dynamics in vivo is influenced by the exit tunnel is poorly understood. Genome-wide ribosome profiling in mammalian cells reveals elevated ribosome density at the start codon and surprisingly the downstream 5th codon position as well. We found that the highly focused ribosomal pausing shortly after initiation is attributed to the geometry of the exit tunnel, as deletion of the loop region from ribosome protein L4 diminishes translational pausing at the 5th codon position. Unexpectedly, the ribosome variant undergoes translational abandonment shortly after initiation, suggesting that there exists an obligatory step between initiation and elongation commitment. We propose that the post-initiation pausing of ribosomes represents an inherent signature of the translation machinery to ensure productive translation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Codon
  • HEK293 Cells
  • Humans
  • Peptide Chain Initiation, Translational / physiology*
  • Ribosomal Proteins / genetics
  • Ribosomes / genetics*

Substances

  • Codon
  • Ribosomal Proteins
  • ribosomal protein L4