GADD34 mRNA turnover controls the molecular memory of cellular stress experience
Magg, V.; Manetto, A.; Kopp, K.; Welsch, J.; Eke, L.; Kallenberger, S. M.; Haucke, V.; Locker, N.; Stoecklin, G.; Ruggieri, A.
Show abstract
The integrated stress response (ISR) is a key cellular signaling pathway activated by environmental alterations that represses protein synthesis to restore homeostasis. To prevent sustained damage, the ISR is counteracted by the upregulation of Growth Arrest and DNA Damage inducible 34 (GADD34), a stress-induced regulatory subunit of protein phosphatase 1 that mediates translation reactivation and stress recovery. Here, we uncover a novel ISR regulatory mechanism that post-transcriptionally controls the stability of PPP1R15A mRNA encoding GADD34. We established that the 3 untranslated region of PPP1R15A mRNA contains an active AU-rich element recognized by proteins of the ZFP36 family, promoting its rapid decay under normal conditions and stabilization for efficient expression of GADD34 in response to stress. We identify the tight temporal control of PPP1R15A mRNA turnover as a key step in establishing the ISR molecular memory, which sets the threshold for cellular responsiveness and mediates adaptation to repeated stress conditions.
Matching journals
The top 2 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Alternative translation initiation produces synaptic organizer proteoforms with distinct localization and functions 95%
- Adaptive translational pausing is a hallmark of the cellular response to severe environmental stress 95%
- ISRIB blunts the integrated stress response by allosterically antagonising the inhibitory effect of phosphorylated eIF2 on eIF2B 95%
Similar papers in this journal
Similar papers in this journal
- A stress-induced Tyrosine tRNA depletion response mediates codon-based translational repression and growth suppression 95%
- eIF3 mRNA selectivity profiling reveals eIF3k as a cancer-relevant regulator of ribosome content 95%
- An alternative UPF1 isoform drives conditional remodeling of nonsense-mediated mRNA decay 95%
Similar papers in this journal
- The integrated stress response remodels the microtubule organizing center to clear unfolded proteins following proteotoxic stress 95%
- Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress 95%
- Dedicated chaperones coordinate co-translational regulation of ribosomal protein production with ribosome assembly to preserve proteostasis 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.