Divergent regulation of protein synthesis in the cytosol and endoplasmic reticulum compartments of mammalian cells.

Published

Journal Article

In eukaryotic cells, mRNAs encoding signal sequence-bearing proteins undergo translation-dependent trafficking to the endoplasmic reticulum (ER), thereby restricting secretory and integral membrane protein synthesis to the ER compartment. However, recent studies demonstrating that mRNAs encoding cytosolic/nucleoplasmic proteins are represented on ER-bound polyribosomes suggest a global role for the ER in cellular protein synthesis. Here, we examined the steady-state protein synthesis rates and compartmental distribution of newly synthesized proteins in the cytosol and ER compartments. We report that ER protein synthesis rates exceed cytosolic protein synthesis rates by 2.5- to 4-fold; yet, completed proteins accumulate to similar levels in the two compartments. These data suggest that a significant fraction of cytosolic proteins undergo synthesis on ER-bound ribosomes. The compartmental differences in steady-state protein synthesis rates correlated with a divergent regulation of the tRNA aminoacylation/deacylation cycle. In the cytosol, two pathways were observed to compete for aminoacyl-tRNAs-protein synthesis and aminoacyl-tRNA hydrolysis-whereas on the ER tRNA deacylation is tightly coupled to protein synthesis. These findings identify a role for the ER in global protein synthesis, and they suggest models where compartmentalization of the tRNA acylation/deacylation cycle contributes to the regulation of global protein synthesis rates.

Full Text

Duke Authors

Cited Authors

  • Stephens, SB; Nicchitta, CV

Published Date

  • February 2008

Published In

Volume / Issue

  • 19 / 2

Start / End Page

  • 623 - 632

PubMed ID

  • 18077556

Pubmed Central ID

  • 18077556

Electronic International Standard Serial Number (EISSN)

  • 1939-4586

International Standard Serial Number (ISSN)

  • 1059-1524

Digital Object Identifier (DOI)

  • 10.1091/mbc.E07-07-0677

Language

  • eng