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RNA metabolism: putting the brake on the UPR
Author(s) -
CarrerasSureda Amado,
Hetz Claudio
Publication year - 2015
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201540227
Subject(s) - endoplasmic reticulum , unfolded protein response , proteostasis , microbiology and biotechnology , nonsense mediated decay , messenger rna , biology , rna , p bodies , crosstalk , rna binding protein , genetics , translation (biology) , gene , physics , rna splicing , optics
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 [1][Karam R, 2015]. NMD is an mRNA quality control mechanism known to destabilize aberrant mRNA s 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 IRE 1, 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.