Research ArticleCell Biology

A protein kinase A–regulated network encodes short- and long-lived cellular memories

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Science Signaling  19 May 2020:
Vol. 13, Issue 632, eaay3585
DOI: 10.1126/scisignal.aay3585

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Remembering stress with PKA

A prior stress can prime organisms to successfully survive subsequent stresses. In yeast, the kinase PKA is inhibited by stress, resulting in changes in gene expression that mediate the general stress response. Using PKA inhibition as a mimic for stress, Jiang et al. examined how yeast encoded the memories of previous stresses. Short-term memory required metabolism of the sugar trehalose and was more sensitive to the amplitude of the stress than its duration. In contrast, long-term memory was sensitive to stress duration and required stress-induced transcription factors and the storage of messenger ribonucleoproteins in granules. These results show how yeast use PKA to “remember” previous exposures to stress in the short term or over a longer period of time.


Cells can store memories of prior experiences to modulate their responses to subsequent stresses, as seen for the protein kinase A (PKA)–mediated general stress response in yeast, which is required for resistance against future stressful conditions. Using microfluidics and time-lapse microscopy, we quantitatively analyzed how the cellular memory of stress adaptation is encoded in single yeast cells. We found that cellular memory was biphasic. Short-lived memory was mediated by trehalose synthase and trehalose metabolism. Long-lived memory was mediated by PKA-regulated stress-responsive transcription factors and cytoplasmic messenger ribonucleoprotein granules. Short- and long-lived memory could be selectively induced by different priming input dynamics. Computational modeling revealed how the PKA-mediated regulatory network could encode previous stimuli into memories with distinct dynamics. This biphasic memory-encoding scheme might represent a general strategy to prepare for future challenges in rapidly changing environments.

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