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Post-transcriptional dynamics and RNA homeostasis in autophagy and cancer

Cell Death & Differentiation (2023)Cite this article

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Abstract

Autophagy is an essential recycling and quality control pathway which preserves cellular and organismal homeostasis. As a catabolic process, autophagy degrades damaged and aged intracellular components in response to conditions of stress, including nutrient deprivation, oxidative and genotoxic stress. Autophagy is a highly adaptive and dynamic process which requires an intricately coordinated molecular control. Here we provide an overview of how autophagy is regulated post-transcriptionally, through RNA processing events, epitranscriptomic modifications and non-coding RNAs. We further discuss newly revealed RNA-binding properties of core autophagy machinery proteins and review recent indications of autophagy’s ability to impact cellular RNA homeostasis. From a physiological perspective, we examine the biological implications of these emerging regulatory layers of autophagy, particularly in the context of nutrient deprivation and tumorigenesis.

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Fig. 1: Autophagy regulation through alternative signaling arms downstream of mTORC1.
Fig. 2: The implications of RNA-binding proteins in autophagy.
Fig. 3: Degradation of RNA-containing substrates by autophagy.
Fig. 4: Non-coding RNAs: regulating the regulators in autophagy.

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Acknowledgements

Figures in this review were created using BioRender.com. We thank Steven E. Reid for critical reading and commenting of the manuscript. This work was supported by the Lundbeck Foundation (R272-2017-3872), the Novo Nordisk Foundation (NNF19OC0057772) and the Danish Cancer Society (R269-A15420 and R209-A13011).

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Authors and Affiliations

  1. Danish Cancer Institute, Copenhagen, Denmark

    Srinivasa Prasad Kolapalli, Thorbjørn M. Nielsen & Lisa B. Frankel

  2. Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark

    Lisa B. Frankel

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  1. Srinivasa Prasad Kolapalli
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  2. Thorbjørn M. Nielsen
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  3. Lisa B. Frankel
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SPK, TMN, and LBF conceived the topic, discussed its contents, and wrote the manuscript.

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Correspondence to Lisa B. Frankel.

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Kolapalli, S.P., Nielsen, T.M. & Frankel, L.B. Post-transcriptional dynamics and RNA homeostasis in autophagy and cancer. Cell Death Differ (2023). https://doi.org/10.1038/s41418-023-01201-5

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  • DOI: https://doi.org/10.1038/s41418-023-01201-5

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