Human Papillomavirus Type 16 Circular RNA Is Barely Detectable for the Claimed Biological Activity
Lulu Yu, Zhi‐Ming Zheng
Abstract
RNA back-splicing is a rare splicing event accounting for <1% of canonical RNA splicing and, thus, is thought to have little or no biological significance. Recently, circular RNAs (circRNAs) from RNA back-splicing have been found widely in cells and tissues and may have a role in modulating RNA transcription, splicing, and interference and antiviral innate immunity. A recent report claimed that the predominant HPV16 E6*I RNA was nuclear and unable to encode E7. Rather, a viral circE7 was responsible for translating the oncoprotein E7 in CaSki cells, a cervical cancer cell line. However, we found that both HPV16 E6*I and circE7 RNAs in CaSki cells are primarily cytoplasmic and that the copy number of viral E6*I RNA is 656 copies per cell, whereas the viral circE7 is only 0.4 copies per cell. Most importantly, we found that the claimed circE7 function resulted from off-target effect on viral E6*I RNA by the small interfering RNA (siRNA) si-circE7 designed to knock down the back-spliced circE7 RNA.