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Review
. 2022 May;13(3):e1689.
doi: 10.1002/wrna.1689. Epub 2021 Aug 31.

A (dis)integrated stress response: Genetic diseases of eIF2α regulators

Alyssa M English  1 , Katelyn M Green  2 , Stephanie L Moon  1
Affiliations
Review

A (dis)integrated stress response: Genetic diseases of eIF2α regulators

Alyssa M English et al. Wiley Interdiscip Rev RNA. 2022 May.

Abstract

The integrated stress response (ISR) is a conserved mechanism by which eukaryotic cells remodel gene expression to adapt to intrinsic and extrinsic stressors rapidly and reversibly. The ISR is initiated when stress-activated protein kinases phosphorylate the major translation initiation factor eukaryotic translation initiation factor 2ɑ (eIF2ɑ), which globally suppresses translation initiation activity and permits the selective translation of stress-induced genes including important transcription factors such as activating transcription factor 4 (ATF4). Translationally repressed messenger RNAs (mRNAs) and noncoding RNAs assemble into cytoplasmic RNA-protein granules and polyadenylated RNAs are concomitantly stabilized. Thus, regulated changes in mRNA translation, stability, and localization to RNA-protein granules contribute to the reprogramming of gene expression that defines the ISR. We discuss fundamental mechanisms of RNA regulation during the ISR and provide an overview of a growing class of genetic disorders associated with mutant alleles of key translation factors in the ISR pathway. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA in Disease and Development > RNA in Disease Translation > Translation Regulation RNA in Disease and Development > RNA in Development.

Keywords: RNA-protein granules; eIF2α; genetic diseases; integrated stress response; translation.

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References

FURTHER READING
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