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Dissecting the oncogenic properties of essential RNA-modifying enzymes: a focus on NAT10

Oncogene volume 43, pages 1077–1086 (2024)Cite this article

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Abstract

Chemical modifications of ribonucleotides significantly alter the physicochemical properties and functions of RNA. Initially perceived as static and essential marks in ribosomal RNA (rRNA) and transfer RNA (tRNA), recent discoveries unveiled a dynamic landscape of RNA modifications in messenger RNA (mRNA) and other regulatory RNAs. These findings spurred extensive efforts to map the distribution and function of RNA modifications, aiming to elucidate their distribution and functional significance in normal cellular homeostasis and pathological states. Significant dysregulation of RNA modifications is extensively documented in cancers, accentuating the potential of RNA-modifying enzymes as therapeutic targets. However, the essential role of several RNA-modifying enzymes in normal physiological functions raises concerns about potential side effects. A notable example is N-acetyltransferase 10 (NAT10), which is responsible for acetylating cytidines in RNA. While emerging evidence positions NAT10 as an oncogenic factor and a potential target in various cancer types, its essential role in normal cellular processes complicates the development of targeted therapies. This review aims to comprehensively analyze the essential and oncogenic properties of NAT10. We discuss its crucial role in normal cell biology and aging alongside its contribution to cancer development and progression. We advocate for agnostic approaches to disentangling the intertwined essential and oncogenic functions of RNA-modifying enzymes. Such approaches are crucial for understanding the full spectrum of RNA-modifying enzymes and imperative for designing effective and safe therapeutic strategies.

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Fig. 1: NAT10 is an essential gene.
Fig. 2: NAT10 is a cancer-promoting factor.
Fig. 3: Structural and molecular functions of NAT10.
Fig. 4: Role of NAT10 in different cellular processes.

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Data availability

All data shown in this manuscript are publicly available at the following databases: MODOMICS [1], DepMap [125], cBioportal [36], The University of ALabama at Birmingham CANcer data analysis portal (UALCAN) [126], AlphaFold [127], and BioGRID [128]. Data were downloaded from the databases, reanalyzed, and graphed using publicly available R packages. All code is available upon request.

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Acknowledgements

This work was supported by the National Cancer Institute (NCI) grant R00CA245035, the American Association for Cancer Research (AACR) award 22-20-01-ARAN, the V Scholar Award V2022-016, and the American Cancer Society Institutional Research Grant IRG-21-144-27.

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Authors and Affiliations

  1. Department of Pharmacology, Northwestern University, Chicago, IL, USA

    Mahmood H. Dalhat, Sharath Narayan, Hannah Serio & Daniel Arango

  2. Driskill Graduate Program in Life Sciences, Northwestern University, Chicago, IL, USA

    Sharath Narayan

  3. Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA

    Daniel Arango

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  1. Mahmood H. Dalhat
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  2. Sharath Narayan
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M.H.D, S.N. and D.A. wrote the first draft. D.A. structured, wrote, and corrected all the sections in the paper. H.S. and D.A. analyzed publicly available data and prepared the figures. M.H.D., S.N, H.S. and D.A. revised the final draft.

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Correspondence to Daniel Arango.

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Dalhat, M.H., Narayan, S., Serio, H. et al. Dissecting the oncogenic properties of essential RNA-modifying enzymes: a focus on NAT10. Oncogene 43, 1077–1086 (2024). https://doi.org/10.1038/s41388-024-02975-9

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