mRNA escape from stress granule sequestration is dictated by localization to the endoplasmic reticulum
File(s)
Accepted version
Author(s)
Unsworth, H
Raguz, S
Edwards, HJ
Higgins, CF
Yaguee, E
Type
Journal Article
Abstract
In mammalian cells, cytotoxic stress triggers several signaling cascades that converge in the phosphorylation of translation initiation factor 2α, shuttling of nuclear RNA-binding proteins such as TIA-1 to the cytoplasm, and aggregation of most cellular mRNAs into TIA-1-containing stress granules (SGs). As a result, protein synthesis is greatly impaired. Here we describe different dynamics of endogenous transcripts according to their cellular location, in response to stress. While cytosolic mRNAs aggregate into SGs, endoplasmic reticulum (ER) -bound transcripts escape sequestration. This has been specifically demonstrated using the multidrug resistance transporter gene (MDR1) as a model and showing that chimeric RNA constructs can be directed to the cytosol or tethered to the ER depending on the nature of the chimera, in response to stress. In addition, polysome profile analyses indicate that, on stress, ribosomes do not disengage from ER-associated transcripts (puromycin insensitive) and recover their translation status faster than SG-targeted cytosolic mRNAs once the stress is lifted. These findings have important implications for cell survival given that many membrane proteins, which are translated at the ER, have important roles in detoxification
Date Issued
2010-09
Date Acceptance
2010-04-22
Citation
FASEB Journal, 2010, 24 (9), pp.3370-3380
ISSN
0892-6638
Publisher
Federation of American Society of Experimental Biology
Start Page
3370
End Page
3380
Journal / Book Title
FASEB Journal
Volume
24
Issue
9
Copyright Statement
© 2010 FASEB.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000281446400025&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biology
Cell Biology
Life Sciences & Biomedicine - Other Topics
membrane proteins
RNA localization
drug resistance
P-glycoprotein
TIA-1
P-GLYCOPROTEIN
TRANSLATION
PROTEINS
CELLS
MEMBRANE
BINDING
CANCER
COMPARTMENT
EXPRESSION
INITIATION
Publication Status
Published
Date Publish Online
2010-05-07