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Invasion by exogenous RNA: cellular defense strategies and implications for RNA inference

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Abstract

Exogenous RNA poses a continuous threat to genome stability and integrity across various organisms. Accumulating evidence reveals complex mechanisms underlying the cellular response to exogenous RNA, including endo-lysosomal degradation, RNA-dependent repression and innate immune clearance. Across a variety of mechanisms, the natural anti-sense RNA-dependent defensive strategy has been utilized both as a powerful gene manipulation tool and gene therapy strategy named RNA-interference (RNAi). To optimize the efficiency of RNAi silencing, a comprehensive understanding of the whole life cycle of exogenous RNA, from cellular entry to its decay, is vital. In this paper, we review recent progress in comprehending the recognition and elimination of foreign RNA by cells, focusing on cellular entrance, intracellular transportation, and immune-inflammatory responses. By leveraging these insights, we highlight the potential implications of these insights for advancing RNA interference efficiency, underscore the need for future studies to elucidate the pathways and fates of various exogenous RNA forms, and provide foundational information for more efficient RNA delivery methods in both genetic manipulation and therapy in different organisms.

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Acknowledgements

This work was supported by funding from: the National Natural Science Foundation of China to YY (Project Number: 32270558), to XC (Project Number: 32270512) and to CW (Project number: 32100382); Young Taishan Scholar Program of Shandong Province to YY; Natural Science Foundation of Jiangsu Province (Project Number: BK20220268) and the Program of Qilu Young Scholars of Shandong University to XC; and the King Saud University, Saudi Arabia (Project number: RSP2023R7).

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Authors and Affiliations

  1. Laboratory of Marine Protozoan Biodiversity and Evolution, Marine College, Shandong University, Weihai, 264209, China

    Danxu Tang, Chundi Wang, Lifang Li & Xiao Chen

  2. Key Laboratory of Evolution and Marine Biodiversity (Ministry of Education) and Institute of Evolution and Marine Biodiversity, Ocean University of China, Qingdao, 266003, China

    Danxu Tang, Yan Liu & Ying Yan

  3. Zoology Department, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia

    Saleh A. Al-Farraj

  4. Suzhou Research Institute, Shandong University, Suzhou, 215123, China

    Xiao Chen

Authors
  1. Danxu Tang
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  2. Yan Liu
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  3. Chundi Wang
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  4. Lifang Li
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  5. Saleh A. Al-Farraj
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  6. Xiao Chen
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  7. Ying Yan
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Contributions

DT: writing the original draft, reviewing and editing the manuscript. YL, CW, and LL: editing the manuscript. SA: language polishing. YY and XC: conceptualization, supervision, writing, reviewing and editing the manuscript. All authors read and approve the final version of the manuscript.

Corresponding authors

Correspondence to Xiao Chen or Ying Yan.

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Animal and human rights statement

We declare that all applicable international, national, and/or institutional guidelines for experimental use of organisms for the study have been followed and all necessary approvals have been obtained (not applicable for review articles).

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Special Topic: EvoDevo.

Edited by Jiamei Li.

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Tang, D., Liu, Y., Wang, C. et al. Invasion by exogenous RNA: cellular defense strategies and implications for RNA inference. Mar Life Sci Technol 5, 573–584 (2023). https://doi.org/10.1007/s42995-023-00209-7

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