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

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. Wang

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Article number2300
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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Oncogene Proteins
coding
cancer
viruses
oncogenes
proteins
Viruses
cytoplasm
cultured cells
Cells
tumors
Neoplasms
Polyribosomes
Herpesviridae
Cell growth
Oncogenes
Heterografts
Northern Blotting
Tumors
cells

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Transforming activity of an oncoprotein-encoding circular RNA from human papillomavirus. / Zhao, Jiawei; Lee, Eunice E.; Kim, Jiwoong; Yang, Rong; Chamseddin, Bahir; Ni, Chunyang; Gusho, Elona; Xie, Yang; Chiang, Cheng Ming; Buszczak, Michael; Zhan, Xiaowei; Laimins, Laimonis; Wang, Richard C.

In: Nature communications, Vol. 10, No. 1, 2300, 01.12.2019.

Research output: Contribution to journalArticle

Zhao, Jiawei ; Lee, Eunice E. ; Kim, Jiwoong ; Yang, Rong ; Chamseddin, Bahir ; Ni, Chunyang ; Gusho, Elona ; Xie, Yang ; Chiang, Cheng Ming ; Buszczak, Michael ; Zhan, Xiaowei ; Laimins, Laimonis ; Wang, Richard C. / Transforming activity of an oncoprotein-encoding circular RNA from human papillomavirus. In: Nature communications. 2019 ; Vol. 10, No. 1.
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