Journal
CELL RESEARCH
Volume 24, Issue 7, Pages 842-851Publisher
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/cr.2014.74
Keywords
ribosome; translation
Categories
Funding
- Genomics Scholar's Award from Center for Vertebrate Genomics at Cornell
- National Institutes of Health [1 DP2 OD006449-01]
- Ellison Medical Foundation [AG-NS-0605-09]
- DOD Exploration-Hypothesis Development Award [W81XWH-11-1-0236]
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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.
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