title: The unfolded protein response triggers selective mRNA release from the endoplasmic reticulum.
abstract: The unfolded protein response (UPR) is a stress response program that reprograms cellular translation and gene expression in response to proteotoxic stress in the endoplasmic reticulum (ER). One of the primary means by which the UPR alleviates this stress is by reducing protein flux into the ER via a general suppression of protein synthesis and ER-specific mRNA degradation. We report here an additional UPR-induced mechanism for the reduction of protein flux into the ER, where mRNAs that encode signal sequences are released from the ER to the cytosol. By removing mRNAs from the site of translocation, this mechanism may serve as a potent means to transiently reduce ER protein folding load and restore proteostasis. These findings identify the dynamic subcellular localization of mRNAs and translation as a selective and rapid regulatory feature of the cellular response to protein folding stress.
authors.affiliation: Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Reid
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore 169857, Singapore.
authors.forename: Angeline S-L
authors.initials: AS
authors.lastname: Tay
authors.affiliation: Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore 169857, Singapore; Program in Neuroscience and Behavioral Disorders, Duke-National University of Singapore Graduate Medical School, Singapore 169857, Singapore.
authors.forename: Shirish
authors.initials: S
authors.lastname: Shenolikar
authors.affiliation: Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: christopher.nicchitta@duke.edu.
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Nicchitta
mesh_terms: D000818:Animals; D003600:Cytosol / Q000378:metabolism; D004229:Dithiothreitol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism*; D005347:Fibroblasts; D007700:Kinetics; D051379:Mice; D016366:Open Reading Frames; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D056811:Unfolded Protein Response
chemical_list: D012333:RNA, Messenger; D004229:Dithiothreitol