The Inevitable Relationship Between Viruses and RNA Modifications Revealed Through Adenovirus Research

Over the past two decades, it has become clear that gene expression in eukaryotic cells is regulated by diverse RNA molecules. In this process, new RNAs have been discovered, and the roles of their modified molecules have been progressively elucidated. In this review, we first describe how RNA and its modifications function in virus-infected cells. We use adenovirus and several other viruses as models during the early stages of infection, which we believe determines the fate of infected cells. Next, we reviewed the process of identifying the early mRNA transcription initiation sites in adenovirus-infected cells. The results showed that the transcription initiation sites for the E1 and E4 mRNAs-known as adenovirus oncogenes-are highly complex. The same level of complexity in transcription initiation sites has been suggested for oncogenes in several other DNA tumor viruses, including SV40, polyomavirus, and papillomavirus. It is now understood that the transcription of the early adenovirus mRNA involves alternative splicing, rather than constitutive splicing, as we previously demonstrated. Furthermore, recent research indicates that the abnormal alternative splicing of intracellular mRNA may induce cellular carcinogenesis. Finally, we discuss whether alternative splicing plays a role in the carcinogenic effects of DNA tumor viruses, such as adenovirus. Additionally, we discuss that alternative splicing plays a crucial role in adenovirus replication.