SRP samples nascent chains for the presence of signal sequences by interacting with ribosomes at a discrete step during translation elongation

Cell. 1995 Jun 30;81(7):1075-84. doi: 10.1016/s0092-8674(05)80012-1.


The signal recognition particle (SRP) binds to ribosomes that synthesize nascent chains bearing signal sequences and catalyzes their targeting to the endoplasmic reticulum membrane. In S. cerevisiae, a temperature-sensitive mutation in the SEC65 gene, encoding an SRP subunit, results in lowered levels of SRP. Growth and protein translocation defects induced by this mutation can be suppressed specifically by sublethal doses of cycloheximide but not anisomycin, each inhibitors of different steps of translation elongation. Cycloheximide also suppresses protein translocation defects caused by depletion of a different SRP subunit. We propose that reduced elongation rates in the presence of cycloheximide allow otherwise insufficient SRP to interact efficiently with ribosomes. These results are consistent with a sampling model in which SRP cycles on and off of translating ribosomes at specific steps during the elongation cycle to inspect all nascent chains for the presence of signal sequences.

Publication types

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

MeSH terms

  • Animals
  • Cycloheximide / pharmacology
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism
  • Fungal Proteins / chemistry*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Genes, Fungal
  • Genotype
  • Kinetics
  • Macromolecular Substances
  • Mammals
  • Mutagenesis
  • Peptide Chain Elongation, Translational*
  • Protein Biosynthesis / drug effects
  • Protein Biosynthesis / physiology*
  • Protein Processing, Post-Translational / drug effects
  • Protein Synthesis Inhibitors / pharmacology
  • Ribosomes / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Signal Recognition Particle / chemistry*
  • Signal Recognition Particle / genetics
  • Signal Recognition Particle / metabolism*
  • Temperature
  • Time Factors


  • Fungal Proteins
  • Macromolecular Substances
  • Protein Synthesis Inhibitors
  • SEC65 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Signal Recognition Particle
  • Cycloheximide