title: Ribosome profiling reveals sequence-independent post-initiation pausing as a signature of translation.
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.
authors.affiliation: 1] Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA [2] Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Han
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Gao
authors.affiliation: Graduate Field of Genetics, Genomics and Development, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Botao
authors.initials: B
authors.lastname: Liu
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Wan
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Xingqian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Shu-Bing
authors.initials: SB
authors.lastname: Qian
mesh_terms: D003062:Codon; D057809:HEK293 Cells; D006801:Humans; D010442:Peptide Chain Initiation, Translational / Q000502:physiology*; D012269:Ribosomal Proteins / Q000235:genetics; D012270:Ribosomes / Q000235:genetics*
chemical_list: D003062:Codon; D012269:Ribosomal Proteins; C056368:ribosomal protein L4