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Media type:
E-Article
Title:
ZBP1 regulates mRNA stability during cellular stress
Contributor:
Stöhr, Nadine;
Lederer, Marcell;
Reinke, Claudia;
Meyer, Sylke;
Hatzfeld, Mechthild;
Singer, Robert H.;
Hüttelmaier, Stefan
Published:
Rockefeller University Press, 2006
Published in:
The Journal of Cell Biology, 175 (2006) 4, Seite 527-534
Language:
English
DOI:
10.1083/jcb.200608071
ISSN:
1540-8140;
0021-9525
Origination:
Footnote:
Description:
An essential constituent of the integrated stress response (ISR) is a reversible translational suppression. This mRNA silencing occurs in distinct cytoplasmic foci called stress granules (SGs), which transiently associate with processing bodies (PBs), typically serving as mRNA decay centers. How mRNAs are protected from degradation in these structures remains elusive. We identify that Zipcode-binding protein 1 (ZBP1) regulates the cytoplasmic fate of specific mRNAs in nonstressed cells and is a key regulator of mRNA turnover during the ISR. ZBP1 association with target mRNAs in SGs was not essential for mRNA targeting to SGs. However, ZBP1 knockdown induced a selective destabilization of target mRNAs during the ISR, whereas forced expression increased mRNA stability. Our results indicate that although targeting of mRNAs to SGs is nonspecific, the stabilization of mRNAs during cellular stress requires specific protein–mRNA interactions. These retain mRNAs in SGs and prevent premature decay in PBs. Hence, mRNA-binding proteins are essential for translational adaptation during cellular stress by modulating mRNA turnover.