Endoplasmic reticulum stress increases AT1R mRNA expression via TIA-1-dependent mechanism

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http://hdl.handle.net/10138/163191

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Backlund , M , Paukku , K , Kontula , K K & Lehtonen , J Y A 2016 , ' Endoplasmic reticulum stress increases AT1R mRNA expression via TIA-1-dependent mechanism ' , Nucleic Acids Research , vol. 44 , no. 7 , pp. 3095-3104 . https://doi.org/10.1093/nar/gkv1368

Title: Endoplasmic reticulum stress increases AT1R mRNA expression via TIA-1-dependent mechanism
Author: Backlund, Michael; Paukku, Kirsi; Kontula, Kimmo K.; Lehtonen, Jukka Y. A.
Contributor: University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Kimmo Kontula Research Group
Date: 2016-04-20
Language: eng
Number of pages: 10
Belongs to series: Nucleic Acids Research
ISSN: 0305-1048
URI: http://hdl.handle.net/10138/163191
Abstract: As the formation of ribonucleoprotein complexes is a major mechanism of angiotensin II type 1 receptor (AT1R) regulation, we sought to identify novel AT1R mRNA binding proteins. By affinity purification and mass spectroscopy, we identified TIA-1. This interaction was confirmed by colocalization of AT1R mRNA and TIA-1 by FISH and immunofluorescence microscopy. In immunoprecipitates of endogenous TIA-1, reverse transcription-PCR amplified AT1R mRNA. TIA-1 has two binding sites within AT1R 3'-UTR. The binding site proximal to the coding region is glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-dependent whereas the distal binding site is not. TIA-1 functions as a part of endoplasmic reticulum (ER) stress response leading to stress granule (SG) formation and translational silencing. We and others have shown that AT1R expression is increased by ER stress-inducing factors. In unstressed cells, TIA-1 binds to AT1R mRNA and decreases AT1R protein expression. Fluorescence microscopy shows that ER stress induced by thapsigargin leads to the transfer of TIA-1 to SGs. In FISH analysis AT1R mRNA remains in the cytoplasm and no longer colocalizes with TIA-1. Thus, release of TIA-1-mediated suppression by ER stress increases AT1R protein expression. In conclusion, AT1R mRNA is regulated by TIA-1 in a ER stress-dependent manner.
Subject: TYPE-1 RECEPTOR EXPRESSION
ARTERY ENDOTHELIAL-CELLS
ANGIOTENSIN-II RECEPTOR
OXIDATIVE STRESS
MYOCARDIAL-INFARCTION
PROTEIN TRANSLATION
UP-REGULATION
KAPPA-B
GRANULES
TIA-1
1182 Biochemistry, cell and molecular biology
3121 General medicine, internal medicine and other clinical medicine
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