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Regulation of long non-coding RNAs and genome dynamics by the RNA surveillance machinery

Nature Reviews Molecular Cell Biology volume 21, pages 123–136 (2020)Cite this article

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Abstract

Much of the mammalian genome is transcribed, generating long non-coding RNAs (lncRNAs) that can undergo post-transcriptional surveillance whereby only a subset of the non-coding transcripts is allowed to attain sufficient stability to persist in the cellular milieu and control various cellular functions. Paralleling protein turnover by the proteasome complex, lncRNAs are also likely to exist in a dynamic equilibrium that is maintained through constant monitoring by the RNA surveillance machinery. In this Review, we describe the RNA surveillance factors and discuss the vital role of lncRNA surveillance in orchestrating various biological processes, including the protection of genome integrity, maintenance of pluripotency of embryonic stem cells, antibody–gene diversification, coordination of immune cell activation and regulation of heterochromatin formation. We also discuss examples of human diseases and developmental defects associated with the failure of RNA surveillance mechanisms, further highlighting the importance of lncRNA surveillance in maintaining cell and organism functions and health.

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Fig. 1: Transcription-associated RNA surveillance.
Fig. 2: RNA surveillance between deleterious and programmed DNA mutagenesis.
Fig. 3: Functions of RNA surveillance in DNA damage repair and chromatin biology.
Fig. 4: The biological relevance of RNA surveillance.

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Acknowledgements

The authors thank many colleagues in the field of RNA biology for exciting discussions that contributed to some of the ideas expressed in this article, and G. Rothschild for proofreading the manuscript. The authors apologize to the many colleagues whose work they were not able to cover in this article owing to limitations of space and scope. This work was supported by grants to U.B. (NIAID 1R01AI099195 and R01AI134988), Leukemia & Lymphoma Society, and the Pershing Square Sohn Cancer Research Alliance. L.N. is supported by an NIH grant (T32 AI106711).

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  1. Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA

    Lekha Nair, Hachung Chung & Uttiya Basu

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Nair, L., Chung, H. & Basu, U. Regulation of long non-coding RNAs and genome dynamics by the RNA surveillance machinery. Nat Rev Mol Cell Biol 21, 123–136 (2020). https://doi.org/10.1038/s41580-019-0209-0

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