High-Resolution Ribosome Profiling for Determining Ribosome Functional States During Translation Elongation

Methods Mol Biol. 2022:2428:173-186. doi: 10.1007/978-1-0716-1975-9_11.

Abstract

Translation elongation is a highly choreographed process that involves substantial conformational changes of the ribosome to accommodate aminoacyl-tRNAs and traverse along the mRNA template. To capture distinct functional states of the ribosome, a high-resolution ribosome profiling-based approach has been developed. By deep-sequencing differently sized ribosome-protected mRNA fragments, this approach captures not only ribosome positions but also their functional states in vivo across the Saccharomyces cerevisiae transcriptome with codon resolution. This chapter presents a condensed and step-by-step protocol for preserving ribosomes in their functional states using a cocktail of antibiotics that traps distinct steps of elongating ribosomes and for constructing a cDNA library derived from the ribosome-protected mRNA fragments for deep sequencing.

Keywords: Elongation regulation; High-resolution ribosome profiling; Ribosome functional states.

Publication types

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

MeSH terms

  • Codon / metabolism
  • Peptide Chain Elongation, Translational*
  • Protein Biosynthesis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ribosomes* / genetics
  • Ribosomes* / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism

Substances

  • Codon
  • RNA, Messenger