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HBV pgRNA can generate a circRNA with two junction sites

By Min Zhu, Zi Liang, Jun Pan, Xiaolong Hu, Xing Zhang, Renyu Xue, Guangli Cao, Chengliang Gong

Posted 15 May 2020
bioRxiv DOI: 10.1101/2020.05.14.095273

To verify whether Hepatitis B virus (HBV) can form circRNA, the circRNA sequencing results of the HBV−positive HepG 2.2.15 hepatocarcinoma cell line were compared with the HBV genome. A novel circRNA, named as HBV\_circ\_1, was mapped to the 489−2985 nt region of the HBV genome (GenBank accession No. [KU668446.1][1]), which was derived from HBV pgRNA and has two junction sites. A partial fragment of the pgRNA (corresponding to HBV DNA genome 489−3,182−2,985nt) was resected and then connected to form a junction site of HBV\_circ\_1 (corresponding to HBV DNA genome 489/2985nt). The 5′−terminal region (corresponding to HBV DNA genome 1,820−1,932nt) of pgRNA was repeated with the region of pgRNA at the 3′−terminal region. Another junction site of HBV\_circ\_1 (corresponding to HBV DNA genome 1820nt) was formed in a manner similar to DNA homologous recombination mediated by repeats of pgRNA. Moreover, this RNA homologous recombination mediated by the repeats of pgRNA does not have tissue specificity and genus specificity. Reverse transcription PCR, northern blotting, and tissue in situ hybridization confirmed the existence of HBV\_circ\_1 in HepG2.2.15 cells and HBV related hepatocellular carcinoma (HCC) tissue. This study expands our understanding of circRNA generation mechanisms, and provide a new perspective for understanding the molecular pathogenesis of the virus. ### Competing Interest Statement The authors have declared no competing interest. [1]: /lookup/external-ref?link_type=GEN&access_num=KU668446.1&atom=%2Fbiorxiv%2Fearly%2F2020%2F05%2F15%2F2020.05.14.095273.atom

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