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The cellular and KSHV A-to-I RNA editome in primary effusion lymphoma and its role in the viral lifecycle

Author

Listed:
  • Suba Rajendren

    (Vanderbilt University Medical Center
    Immunology and Inflammation
    Vanderbilt Center for Immunobiology)

  • Xiang Ye

    (Vanderbilt University Medical Center
    Immunology and Inflammation
    Vanderbilt Center for Immunobiology)

  • William Dunker

    (Vanderbilt University Medical Center
    Immunology and Inflammation
    Vanderbilt Center for Immunobiology)

  • Antiana Richardson

    (Vanderbilt University Medical Center
    Immunology and Inflammation
    Vanderbilt Center for Immunobiology)

  • John Karijolich

    (Vanderbilt University Medical Center
    Immunology and Inflammation
    Vanderbilt Center for Immunobiology
    Vanderbilt University School of Medicine)

Abstract

Adenosine-to-inosine RNA editing is a major contributor to transcriptome diversity in animals with far-reaching biological consequences. Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of several human malignancies including primary effusion lymphoma (PEL). The extent of RNA editing within the KSHV transcriptome is unclear as is its contribution to the viral lifecycle. Here, we leverage a combination of biochemical and genomic approaches to determine the RNA editing landscape in host- and KSHV transcriptomes during both latent and lytic replication in PEL. Analysis of RNA editomes reveals it is dynamic, with increased editing upon reactivation and the potential to deregulate pathways critical for latency and tumorigenesis. In addition, we identify conserved RNA editing events within a viral microRNA and discover their role in miRNA biogenesis as well as viral infection. Together, these results describe the editome of PEL cells as well as a critical role for A-to-I editing in the KSHV lifecycle.

Suggested Citation

  • Suba Rajendren & Xiang Ye & William Dunker & Antiana Richardson & John Karijolich, 2023. "The cellular and KSHV A-to-I RNA editome in primary effusion lymphoma and its role in the viral lifecycle," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37105-8
    DOI: 10.1038/s41467-023-37105-8
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    References listed on IDEAS

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    1. Colleen M. Burns & Hsin Chu & Susan M. Rueter & Linda K. Hutchinson & Hervé Canton & Elaine Sanders-Bush & Ronald B. Emeson, 1997. "Regulation of serotonin-2C receptor G-protein coupling by RNA editing," Nature, Nature, vol. 387(6630), pages 303-308, May.
    2. Julie M. Eggington & Tom Greene & Brenda L. Bass, 2011. "Predicting sites of ADAR editing in double-stranded RNA," Nature Communications, Nature, vol. 2(1), pages 1-9, September.
    3. Jae Hoon Bahn & Jaegyoon Ahn & Xianzhi Lin & Qing Zhang & Jae-Hyung Lee & Mete Civelek & Xinshu Xiao, 2015. "Genomic analysis of ADAR1 binding and its involvement in multiple RNA processing pathways," Nature Communications, Nature, vol. 6(1), pages 1-13, May.
    4. Yang Zhao & Xiang Ye & William Dunker & Yu Song & John Karijolich, 2018. "RIG-I like receptor sensing of host RNAs facilitates the cell-intrinsic immune response to KSHV infection," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
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