title: Stable ribosome binding to the endoplasmic reticulum enables compartment-specific regulation of mRNA translation.
abstract: 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.
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Samuel B
authors.initials: SB
authors.lastname: Stephens
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Dodd
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Brewer
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Lager
authors.forename: Jack D
authors.initials: JD
authors.lastname: Keene
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Nicchitta
mesh_terms: D000818:Animals; D002458:Cell Fractionation; D045744:Cell Line, Tumor; D003545:Cysteine / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D008715:Methionine / Q000378:metabolism; D051379:Mice; D010954:Plasmacytoma; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics*; D012270:Ribosomes / Q000378:metabolism* / Q000648:ultrastructure; D014461:Ultracentrifugation
chemical_list: D012333:RNA, Messenger; D008715:Methionine; D003545:Cysteine