Stable ribosome binding to the endoplasmic reticulum enables compartment-specific regulation of mRNA translation.
Published
Journal Article
In eukaryotic cells, protein synthesis is compartmentalized; mRNAs encoding secretory/membrane proteins are translated on endoplasmic reticulum (ER)-bound ribosomes, whereas mRNAs encoding cytosolic proteins are translated on free ribosomes. mRNA partitioning between the two compartments occurs via positive selection: free ribosomes engaged in the translation of signal sequence-encoding mRNAs are trafficked from the cytosol to the ER. After translation termination, ER-bound ribosomes are thought to dissociate, thereby completing a cycle of mRNA partitioning. At present, the physiological basis for termination-coupled ribosome release is unknown. To gain insight into this process, we examined ribosome and mRNA partitioning during the unfolded protein response, key elements of which include suppression of the initiation stage of protein synthesis and polyribosome breakdown. We report that unfolded protein response (UPR)-elicited polyribosome breakdown resulted in the continued association, rather than release, of ER-bound ribosomes. Under these conditions, mRNA translation in the cytosol was suppressed, whereas mRNA translation on the ER was sustained. Furthermore, mRNAs encoding key soluble stress proteins (XBP-1 and ATF-4) were translated primarily on ER-bound ribosomes. These studies demonstrate that ribosome release from the ER is termination independent and identify new and unexpected roles for the ER compartment in the translational response to induction of the unfolded protein response.
Full Text
Duke Authors
Cited Authors
- Stephens, SB; Dodd, RD; Brewer, JW; Lager, PJ; Keene, JD; Nicchitta, CV
Published Date
- December 2005
Published In
Volume / Issue
- 16 / 12
Start / End Page
- 5819 - 5831
PubMed ID
- 16221886
Pubmed Central ID
- 16221886
International Standard Serial Number (ISSN)
- 1059-1524
Digital Object Identifier (DOI)
- 10.1091/mbc.e05-07-0685
Language
- eng
Conference Location
- United States