ZBP1 regulates mRNA stability during cellular stress

Nadine Stöhr, Marcell Lederer, Claudia Reinke, Sylke Meyer, Mechthild Hatzfeld, Robert H. Singer, Stefan Hüttelmaier

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)527-534
Number of pages8
JournalJournal of Cell Biology
Volume175
Issue number4
DOIs
StatePublished - Nov 20 2006

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RNA Stability
Carrier Proteins
Messenger RNA

ASJC Scopus subject areas

  • Cell Biology

Cite this

Stöhr, N., Lederer, M., Reinke, C., Meyer, S., Hatzfeld, M., Singer, R. H., & Hüttelmaier, S. (2006). ZBP1 regulates mRNA stability during cellular stress. Journal of Cell Biology, 175(4), 527-534. https://doi.org/10.1083/jcb.200608071

ZBP1 regulates mRNA stability during cellular stress. / Stöhr, Nadine; Lederer, Marcell; Reinke, Claudia; Meyer, Sylke; Hatzfeld, Mechthild; Singer, Robert H.; Hüttelmaier, Stefan.

In: Journal of Cell Biology, Vol. 175, No. 4, 20.11.2006, p. 527-534.

Research output: Contribution to journalArticle

Stöhr, N, Lederer, M, Reinke, C, Meyer, S, Hatzfeld, M, Singer, RH & Hüttelmaier, S 2006, 'ZBP1 regulates mRNA stability during cellular stress', Journal of Cell Biology, vol. 175, no. 4, pp. 527-534. https://doi.org/10.1083/jcb.200608071
Stöhr N, Lederer M, Reinke C, Meyer S, Hatzfeld M, Singer RH et al. ZBP1 regulates mRNA stability during cellular stress. Journal of Cell Biology. 2006 Nov 20;175(4):527-534. https://doi.org/10.1083/jcb.200608071
Stöhr, Nadine ; Lederer, Marcell ; Reinke, Claudia ; Meyer, Sylke ; Hatzfeld, Mechthild ; Singer, Robert H. ; Hüttelmaier, Stefan. / ZBP1 regulates mRNA stability during cellular stress. In: Journal of Cell Biology. 2006 ; Vol. 175, No. 4. pp. 527-534.
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