Profiling of Small Ribosomal Subunits Reveals Modes and Regulation of Translation Initiation

Adam Giess, Yamila N. Torres Cleuren, Håkon Tjeldnes, Maximilian Krause, Teshome Tilahun Bizuayehu, Senna Hiensch, Aniekan Okon, Carston R. Wagner, Eivind Valen

Research output: Contribution to journalArticle

Abstract

Translation initiation is often attributed as the rate-determining step of eukaryotic protein synthesis and key to gene expression control. Despite this centrality, the series of steps involved in this process is poorly understood. Here, we capture the transcriptome-wide occupancy of ribosomes across all stages of translation initiation, enabling us to characterize the transcriptome-wide dynamics of ribosome recruitment to mRNAs, scanning across 5′ UTRs and stop codon recognition, in a higher eukaryote. We provide mechanistic evidence for ribosomes attaching to the mRNA by threading the mRNA through the small subunit. Moreover, we identify features that regulate the recruitment and processivity of scanning ribosomes and redefine optimal initiation contexts. Our approach enables deconvoluting translation initiation into separate stages and identifying regulators at each step.

Original languageEnglish (US)
Article number107534
JournalCell reports
Volume31
Issue number3
DOIs
StatePublished - Apr 21 2020

Keywords

  • Kozak sequence
  • RNA
  • initiation
  • next-generation sequencing
  • ribosome profiling
  • ribosome recruitment
  • scanning processivity
  • small ribosomal subunit (SSU)
  • translation
  • uORF

PubMed: MeSH publication types

  • Journal Article

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  • Cite this

    Giess, A., Torres Cleuren, Y. N., Tjeldnes, H., Krause, M., Bizuayehu, T. T., Hiensch, S., Okon, A., Wagner, C. R., & Valen, E. (2020). Profiling of Small Ribosomal Subunits Reveals Modes and Regulation of Translation Initiation. Cell reports, 31(3), [107534]. https://doi.org/10.1016/j.celrep.2020.107534