A

Human Polyomavirus-Encoded Circular RNAs

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

ABSTRACT Circular RNAs (circRNAs) are a conserved class of RNAs with diverse functions. A subset of circRNAs are translated into peptides. Here we describe circular RNAs encoded by human polyomaviruses (HPyVs), including circular forms of RNAs encoding variants of the previously described alternative large T antigen open reading frame (ALTO) gene. Circular ALTO RNAs (circALTOs) can be detected in virus positive Merkel cell carcinoma (VP-MCC) cell lines and tumor samples. CircALTOs are stable, predominantly located in the cytoplasm, and N 6 -methyladenosine (m 6 A) modified. MCPyV circALTOs produce ALTO protein in cultured cells. MCPyV ALTO promotes the transcription of co-transfected reporter genes. MCPyV circALTOs are enriched in exosomes derived from VP-MCC lines and circALTO-transfected 293T cells, and purified exosomes can mediate ALTO expression and transcriptional activation. The related trichodysplasia spinulosa polyomavirus (TSPyV) also expresses a circALTO that can be detected in infected tissues and produces ALTO protein in cultured cells. Thus, human polyomavirus circRNAs are expressed in human tumors and tissues, encode for proteins, and may contribute to the infectious and tumorigenic properties of these viruses.

Authors 13

  1. The University of Texas Southwestern Medical Center

    Affiliation as printed

    Department of Dermatology, UT Southwestern Medical Center, Dallas, TX, USA

  2. The University of Texas Southwestern Medical Center

    Affiliation as printed

    Department of Dermatology, UT Southwestern Medical Center, Dallas, TX, USA

  3. The University of Texas Southwestern Medical Center

    Affiliation as printed

    Quantitative Biomedical Research Center, Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, TX, USA

  4. The University of Texas at Austin

    Affiliation as printed

    Department of Molecular Biosciences, University of Texas, Austin, TX, USA

  5. The University of Texas at Austin

    Affiliation as printed

    Department of Molecular Biosciences, University of Texas, Austin, TX, USA

  6. The University of Texas Southwestern Medical Center

    Affiliation as printed

    Touchstone Diabetes Center, Department of Internal Medicine, the University of Texas Southwestern Medical Center, Dallas, TX, USA

  7. The University of Texas Southwestern Medical Center

    Affiliation as printed

    Touchstone Diabetes Center, Department of Internal Medicine, the University of Texas Southwestern Medical Center, Dallas, TX, USA

  8. The University of Texas Southwestern Medical Center

    Affiliation as printed

    Department of Dermatology, UT Southwestern Medical Center, Dallas, TX, USA

  9. The University of Texas Southwestern Medical Center

    Affiliation as printed

    Department of Dermatology, UT Southwestern Medical Center, Dallas, TX, USA

  10. Ghent University Hospital

    Affiliation as printed

    Department of Dermatology, Ghent University Hospital, Ghent, Belgium

  11. Leiden University Medical Center

    Affiliation as printed

    Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands

  12. The University of Texas at Austin

    Affiliation as printed

    Department of Molecular Biosciences, University of Texas, Austin, TX, USA

  13. Richard C. Wang corresponding

    Harold C. Simmons Comprehensive Cancer Center · The University of Texas Southwestern Medical Center

    Affiliation as printed

    Department of Dermatology, UT Southwestern Medical Center, Dallas, TX, USA

    Harold C. Simmons Cancer Center, UT Southwestern Medical Center, Dallas, TX, 75390

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References 64