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.
Type
Journal articleSubject
Endoplasmic ReticulumPolyribosomes
Cytosol
Fibroblasts
Animals
Mice
Dithiothreitol
RNA, Messenger
Protein Biosynthesis
Kinetics
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Unfolded Protein Response
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https://hdl.handle.net/10161/17236Published Version (Please cite this version)
10.1016/j.cell.2014.08.012Publication Info
Reid, David W; Chen, Qiang; Tay, Angeline S-L; Shenolikar, Shirish; & Nicchitta, Christopher
V (2014). The unfolded protein response triggers selective mRNA release from the endoplasmic
reticulum. Cell, 158(6). pp. 1362-1374. 10.1016/j.cell.2014.08.012. Retrieved from https://hdl.handle.net/10161/17236.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Christopher Vincent Nicchitta
Professor of Cell Biology
Our laboratory studies the cellular architecture and regulation of protein synthesis,
with the goal of understanding how cells regulate the subcellular organization and
temporal dynamics of protein synthesis. We focus on mRNA localization - the process
by which cells control where and when a protein is synthesized by localizing its mRNA
to a discrete location(s) in the cell. Such regulation is critical for many aspects
of cell dynamics, cell signaling and cell division. Of the diverse mRN
Shirish Shenolikar
Professor Emeritus of Psychiatry and Behavioral Sciences
Protein phosphorylation controls a wide range of physiological processes in mammalian
tissues. Phosphorylation state of cellular proteins is controlled by the opposing
actions of protein kinases and phosphatases that are regulated by hormones, neurotransmitters,
growth factors and other environmental cues. Our research attempts to understand the
communication between protein kinases and phosphatases that dictates cellular protein
phosphorylation and the cell's response to hormones. Over the
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