title: RNA metabolism: putting the brake on the UPR.
abstract: The unfolded protein response (UPR) is a major signaling cascade that determines cell fate under conditions of endoplasmic reticulum (ER) stress. The kinetics and amplitude of UPR responses are tightly controlled by several feedback loops and the expression of positive and negative regulators. In this issue of EMBO Reports, the Wilkinson lab uncovers a novel function of nonsense-mediated RNA decay (NMD) in fine-tuning the UPR. NMD is an mRNA quality control mechanism known to destabilize aberrant mRNAs that contain premature termination codons. In this work, NMD was shown to determine the threshold of stress necessary to activate the UPR, in addition to adjusting the amplitude of downstream responses and the termination phase. These effects were mapped to the control of the mRNA stability of IRE1, a major ER stress transducer. This study highlights the dynamic crosstalk between mRNA metabolism and the proteostasis network demonstrating the physiological relevance of normal mRNA regulation by the NMD pathway.
authors: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile Program of Cellular and Molecular Biology, Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
authors: Amado
authors: A
authors: Carreras-Sureda
authors: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile Program of Cellular and Molecular Biology, Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, University of Chile, Santiago, Chile Department of Immunology and Infectious diseases, Harvard School of Public Health, Boston, MA, USA.
authors: Claudio
authors: C
authors: Hetz
mesh_terms: D000818:Animals; D059365:Nonsense Mediated mRNA Decay; D056811:Unfolded Protein Response / Q000235:genetics*