Fidelity of Cotranslational Protein Targeting to the Endoplasmic Reticulum

Int J Mol Sci. 2021 Dec 28;23(1):281. doi: 10.3390/ijms23010281.


Fidelity of protein targeting is essential for the proper biogenesis and functioning of organelles. Unlike replication, transcription and translation processes, in which multiple mechanisms to recognize and reject noncognate substrates are established in energetic and molecular detail, the mechanisms by which cells achieve a high fidelity in protein localization remain incompletely understood. Signal recognition particle (SRP), a conserved pathway to mediate the localization of membrane and secretory proteins to the appropriate cellular membrane, provides a paradigm to understand the molecular basis of protein localization in the cell. In this chapter, we review recent progress in deciphering the molecular mechanisms and substrate selection of the mammalian SRP pathway, with an emphasis on the key role of the cotranslational chaperone NAC in preventing protein mistargeting to the ER and in ensuring the organelle specificity of protein localization.

Keywords: endoplasmic reticulum; fidelity; membrane proteins; nascent polypeptide-associated complex; protein targeting; ribosome; signal recognition particle.

Publication types

  • Review

MeSH terms

  • Animals
  • Endoplasmic Reticulum / metabolism*
  • Humans
  • Models, Biological
  • Molecular Chaperones / metabolism
  • Protein Biosynthesis*
  • Protein Transport
  • Signal Recognition Particle / metabolism


  • Molecular Chaperones
  • Signal Recognition Particle