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Transforming activity of an oncoprotein-encoding circular RNA from human papillomavirus

Author

Listed:
  • Jiawei Zhao

    (UT Southwestern Medical Center)

  • Eunice E. Lee

    (UT Southwestern Medical Center)

  • Jiwoong Kim

    (UT Southwestern Medical Center)

  • Rong Yang

    (UT Southwestern Medical Center)

  • Bahir Chamseddin

    (UT Southwestern Medical Center)

  • Chunyang Ni

    (UT Southwestern Medical Center)

  • Elona Gusho

    (Northwestern University)

  • Yang Xie

    (UT Southwestern Medical Center)

  • Cheng-Ming Chiang

    (UT Southwestern Medical Center
    UT Southwestern Medical Center
    UT Southwestern Medical Center)

  • Michael Buszczak

    (UT Southwestern Medical Center)

  • Xiaowei Zhan

    (UT Southwestern Medical Center)

  • Laimonis Laimins

    (Northwestern University)

  • Richard C. Wang

    (UT Southwestern Medical Center
    UT Southwestern Medical Center)

Abstract

Single-stranded circular RNAs (circRNAs), generated through ‘backsplicing’, occur more extensively than initially anticipated. The possible functions of the vast majority of circRNAs remain unknown. Virus-derived circRNAs have recently been described in gamma-herpesviruses. We report that oncogenic human papillomaviruses (HPVs) generate circRNAs, some of which encompass the E7 oncogene (circE7). HPV16 circE7 is detectable by both inverse RT-PCR and northern blotting of HPV16-transformed cells. CircE7 is N6-methyladenosine (m6A) modified, preferentially localized to the cytoplasm, associated with polysomes, and translated to produce E7 oncoprotein. Specific disruption of circE7 in CaSki cervical carcinoma cells reduces E7 protein levels and inhibits cancer cell growth both in vitro and in tumor xenografts. CircE7 is present in TCGA RNA-Seq data from HPV-positive cancers and in cell lines with only episomal HPVs. These results provide evidence that virus-derived, protein-encoding circular RNAs are biologically functional and linked to the transforming properties of some HPV.

Suggested Citation

  • Jiawei Zhao & Eunice E. Lee & Jiwoong Kim & Rong Yang & Bahir Chamseddin & Chunyang Ni & Elona Gusho & Yang Xie & Cheng-Ming Chiang & Michael Buszczak & Xiaowei Zhan & Laimonis Laimins & Richard C. Wa, 2019. "Transforming activity of an oncoprotein-encoding circular RNA from human papillomavirus," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10246-5
    DOI: 10.1038/s41467-019-10246-5
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    Cited by:

    1. Shaomin Yang & Di Cao & Dabbu Kumar Jaijyan & Mei Wang & Jian Liu & Ruth Cruz-cosme & Songbin Wu & Jiabin Huang & Mulan Zeng & Xiaolian Liu & Wuping Sun & Donglin Xiong & Qiyi Tang & Lizu Xiao & Hua Z, 2024. "Identification and characterization of Varicella Zoster Virus circular RNA in lytic infection," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Junshang Ge & Yi Meng & Jiayue Guo & Pan Chen & Jie Wang & Lei Shi & Dan Wang & Hongke Qu & Pan Wu & Chunmei Fan & Shanshan Zhang & Qianjin Liao & Ming Zhou & Bo Xiang & Fuyan Wang & Ming Tan & Zhaoji, 2024. "Human papillomavirus-encoded circular RNA circE7 promotes immune evasion in head and neck squamous cell carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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