QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 16, Issue 12, 5819-5831, December 2005

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E05-07-0685v1 16/12/5819    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stephens, S. B. Articles by Nicchitta, C. V. Search for Related Content PubMed PubMed Citation Articles by Stephens, S. B. Articles by Nicchitta, C. V.

Stable Ribosome Binding to the Endoplasmic Reticulum Enables Compartment-specific Regulation of mRNA Translation

Samuel B. Stephens ^*, Rebecca D. Dodd ^*, Joseph W. Brewer , Patrick J. Lager , Jack D. Keene , and Christopher V. Nicchitta ^*

^* Department of Cell Biology, Duke University Medical Center, Durham, NC 27710; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710; and Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153

Submitted July 28, 2005; Accepted September 29, 2005
Monitoring Editor: Jeffrey Brodsky

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.

Abbreviations used: DTT, dithiothreitol; eIF2, eukaryotic initiation factor 2; ER, endoplasmic reticulum; PERK, RNA-activated protein kinase-like endoplasmic reticulum kinase; poly(A), polyadenylic acid; poly(I), polyinosinic acid; poly(U), polyuridylic acid; RNP, ribonuclear particle; SRP, signal recognition particle.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Christopher V. Nicchitta (c.nicchitta{at}cellbio.duke.edu).

This article has been cited by other articles:

				B. Pyhtila, T. Zheng, P. J. Lager, J. D. Keene, M. C. Reedy, and C. V. Nicchitta Signal sequence- and translation-independent mRNA localization to the endoplasmic reticulum RNA, March 1, 2008; 14(3): 445 - 453. [Abstract] [Full Text] [PDF]

				S. B. Stephens and C. V. Nicchitta Divergent Regulation of Protein Synthesis in the Cytosol and Endoplasmic Reticulum Compartments of Mammalian Cells Mol. Biol. Cell, February 1, 2008; 19(2): 623 - 632. [Abstract] [Full Text] [PDF]

				W.H. D. Townley-Tilson, S. A. Pendergrass, W. F. Marzluff, and M. L. Whitfield Genome-wide analysis of mRNAs bound to the histone stem-loop binding protein RNA, October 1, 2006; 12(10): 1853 - 1867. [Abstract] [Full Text] [PDF]

				M. Latreille and L. Larose Nck in a Complex Containing the Catalytic Subunit of Protein Phosphatase 1 Regulates Eukaryotic Initiation Factor 2{alpha} Signaling and Cell Survival to Endoplasmic Reticulum Stress J. Biol. Chem., September 8, 2006; 281(36): 26633 - 26644. [Abstract] [Full Text] [PDF]

				S. H. Back, K. Lee, E. Vink, and R. J. Kaufman Cytoplasmic IRE1{alpha}-mediated XBP1 mRNA Splicing in the Absence of Nuclear Processing and Endoplasmic Reticulum Stress J. Biol. Chem., July 7, 2006; 281(27): 18691 - 18706. [Abstract] [Full Text] [PDF]

				S.-B. Qian, E. Reits, J. Neefjes, J. M. Deslich, J. R. Bennink, and J. W. Yewdell Tight Linkage between Translation and MHC Class I Peptide Ligand Generation Implies Specialized Antigen Processing for Defective Ribosomal Products J. Immunol., July 1, 2006; 177(1): 227 - 233. [Abstract] [Full Text] [PDF]

				R. S. Lerner and C. V. Nicchitta mRNA translation is compartmentalized to the endoplasmic reticulum following physiological inhibition of cap-dependent translation RNA, May 1, 2006; 12(5): 775 - 789. [Abstract] [Full Text] [PDF]